tbuckley/cabot-search huggingface dataset:
An in vitro model for cytogenetic conversion in CML. Interferon-alpha preferentially inhibits the outgrowth of malignant stem cells preserved in long-term culture.
Authors: J J Cornelissen, R E Ploemacher, B W Wognum, A Borsboom, H C Kluin-Nelemans, A Hagemeijer, B Löwenberg
Journal: Journal of Clinical Investigation (1998)

IFN-alpha has been shown to prolong survival in chronic myeloid leukemia patients, but its mechanism of action is still not understood. The human cobblestone area-forming cell (CAFC) assay allows for the measurement of the concentration of normal as well as malignant stem cells, while their progeny can be measured in parallel long-term culture (LTC) in flasks. Using CAFC and LTC assays, we have examined direct effects of IFN-alpha (500; 5,000 IU/ml) on the maintenance and outgrowth of CD34-enriched normal and malignant stem cells, obtained from six patients with an established major cytogenetic response to IFN-alpha and from four nonresponding patients. CAFC concentrations were not affected by IFN-alpha. In contrast, IFN-alpha strongly inhibited the clonogenic output in flask LTC. Nucleated cells (NC) produced in LTC were evaluated by fluorescent in situ hybridization (FISH) for the presence of the Philadelphia (Ph) translocation. After 8 wk of LTC, the percentage of Ph+ NCs produced was significantly more inhibited by IFN-alpha in responding patients than in nonresponders. Control LTC without IFN-alpha showed no significant differences of Ph+ NC production between responders and nonresponders. These findings provide the first in vitro model for cytogenetic conversion and suggest that direct antiproliferative effects of IFN-alpha account for the cytogenetic response observed clinically.
Changes in lipoprotein subfractions during diet-induced and exercise-induced weight loss in moderately overweight men.
Authors: P T Williams, R M Krauss, K M Vranizan, P D Wood
Journal: Circulation (1990)

We studied separately the effects of weight loss by calorie restriction (dieting) and by calorie expenditure (primarily, running) on lipoprotein subfraction concentrations in sedentary, moderately overweight men assigned at random into three groups as follows: exercise without calorie restriction (n = 46), calorie restriction without exercise (n = 42), and control (n = 42). Plasma lipoprotein mass concentrations were measured by analytic ultracentrifugation for flotation rates (F0(1.20), S0f) within high density lipoprotein (HDL) (F0(1.20) 0-9), low density lipoprotein (LDL) (S0f 0-12), intermediate density lipoprotein (IDL) (S0f 12-20), and very low density lipoprotein (VLDL) (S0f 20-400) particle distributions. Particle diameter and flotation rate of the most abundant LDL species were determined by nondenaturing polyacrylamide gradient gel electrophoresis and analytic ultracentrifugation, respectively. During the 1-year trial, the exercisers ran (mean +/- SD) 15.6 +/- 9.1 km/wk, and the dieters ate 340 +/- 71 fewer kilocalories per day than at baseline. Total body weight was reduced significantly more in dieters (-7.2 +/- 4.1 kg) and exercisers (-4.0 +/- 3.9 kg) than controls (0.6 +/- 3.7 kg). As compared with mean changes in controls, the exercisers and dieters significantly increased HDL2 mass (48.6% and 47.1%, respectively), decreased VLDL mass (-23.9% and -25.5%), and increased LDL peak particle diameter (2.4 and 3.2 A). When adjusted to an equivalent change in body mass index by analysis of covariance, 1) exercise-induced and diet-induced weight loss produced comparable mean changes in the mass of small LDL and VLDL, and in LDL peak particle diameter; 2) the exercisers versus control group difference in HDL2 was attributed to the exercisers' reduced body mass index; and 3) HDL2 increased significantly less in dieters than in exercisers. In dieters, low calorie intake might mitigate the effects of weight loss on HDL2.
Assessment of Diabetes Continuing Medical Education
Authors: T Elaine Adamson, David S Gullion
Journal: Diabetes Care (1986)

A diabetes professional education program was conducted and evaluated with 31 physicians from a rural/suburban community. Treatment guidelines were established by diabetes experts and community practitioners. To document effectiveness, medical record and survey data on 397 patients of the physicians were collected before and after the program. Each participant received a profile of their baseline performance as compared with peers as part of the educational program. A syllabus was designed to complement both the treatment guidelines and the findings from the baseline data. A telephone conference call with a diabetes consultant also occurred. A comparison between data collected before and after the program showed no significant differences in blood glucose levels or hospitalization rates. Physicians were more likely to recommend self-monitoring of blood glucose (SMBG) (7% versus 20%, P less than 0.05) and to examine their patients' feet (47% versus 73%, P less than 0.05) after the program. More patient education was available in the office (53% versus 73%). Patients using insulin were more likely to test urine for ketones (48% versus 61%, P less than 0.05) and know that decreased sensation in the feet could lead to injury (42% versus 53%, P less than 0.05). However, no improvements were noted in monitoring other complications, regulating diet, or in most aspects of patient education after the program. The results indicated the need for increased emphasis on the value of brief appropriate examinations for monitoring complications of diabetes and the need for physicians to learn techniques for counseling patients in self-management as well as to refer their patients to educational resources.
Vaginal Spermicides and Congenital Disorders: Study Reassessed, Not Retracted
Authors: Micheal B. Bracken
Journal: JAMA (1987)

In 1981 an article by H. Jick and others appeared in The Journal of the American Medical Association concerning a purported link between spermicides and congenital malformations in offspring.  2 of the authors recently retracted their positions taken in the article but Jick and 2 other authors persist in claiming that despite the lack of definitive proof evidence points to a link between vaginal spermicides and trisomies chromosomal abnormalities resulting in such disorders as Down Syndrome.  Studies using chromosome bonding indicate that approximately 25% of trisomies are due to meiotic errors in male gametogenesis which occurs prior to ejaculation and before any possible contact between sperm and spermicides.  Among female meiotic errors 75% (56% of all trisomies) occur during meiosis 1 which is completed prior to ovulation and before direct contact with spermicides.  Maternal meiosis 2 errors in which account for about 19% of all trisomies starts before the sperm fuses with the ovum and continues through development of the female pronucleus after the sperm has contacted the ovum.  In light of the dozens of biochemical changes that occur in the ovum once contact with a sperm has been achieved it is difficult to understand why meiosis 2 should be selectively interfered with by spermicides or how such exposure might happen.  Virtually no trisomies occur at fertilization itself and even if a sperm could survive contact with spermicide a spermicide-damaged sperm would be highly unlikely to achieve fertilization.  The biologic basis for an association of spermicides with chromosome anomalies is quite small.  (authors modified)
Dukes's classification: a valid prognostic indicator for gastric cancer.
Authors: Y Adachi, M Mori, Y Maehara, K Sugimachi
Journal: Gut (1994)

Dukes's classification for colorectal cancer is simple, and correlates well with survival. This study assessed whether the principles of Dukes's classification applied to gastric cancer resulted in the separation of prognostically useful groups. The cumulative survival curves determined by Dukes's, Astler-Coller's (another classification for colorectal cancer), and the Japanese classification for gastric cancer were evaluated using 476 curatively treated patients with gastric cancer. Of the three staging systems, both Dukes's and the Japanese classifications showed a step-wise relationship between the stage of the tumour and the survival of patients. The prognostic value of Dukes's classification was reinforced when Dukes's C cases were subdivided according to the number of positive nodes (1-6 v > or = 7) or the level of positive nodes (n1 v n2,n3) but not when the subdivision was made according to the depth of wall invasion. A modified Dukes's classification in which Dukes's cases are subdivided according to the number of metastatic nodes (Dukes's Ca = 1-6 nodes, Dukes's Cb > 6 nodes) could be both simply and accurately applied to gastric cancer.
Immunosuppressive therapy after human lung transplantation
Authors: C. Knoop, A. Haverich, S. Fischer
Journal: European Respiratory Journal (2003)

In 2002, equal numbers of lung transplantation (LTx) were performed with or without induction therapy with antilymphocyte antibodies, monoclonal anti-CD3 antibody or anti-interleukin‐2‐receptor monoclonal antibodies. It remains to be established if induction therapy after LTx is beneficial or deleterious for long-term graft and patient survival. The vast majority of lung transplant recipients receive a triple-drug maintenance regimen including a calcineurin inhibitor, a cell-cycle inhibitor and steroids. Equal proportions receive cyclosporin A (CsA) and tacrolimus (Tac). There is also a trend to prescribe mycophenolate mofetil (MMF) instead of azathioprine (Aza). Steroid withdrawal is uncommon even 5 yrs after transplantation. The superiority of Tac over CsA as a maintenance agent has not been established to date, and the administration of MMF instead of Aza in combination with CsA and steroids did not improve graft or patient survival in a recent international, prospective, randomised, controlled trial. Shift from cyclosporin A to tacrolimus has emerged as the first treatment step of refractory acute rejection followed by high-dose steroids or antilymphocyte agents, total lymphoid irradiation or photopheresis. The treatment of chronic rejection remains deceptive and includes varied strategies such as modification of the maintenance regimen, addition of inhaled immunosuppressants and/or total lymphoid irradiation and photopheresis.
C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia
Authors: Meritxell Alberich-Jordà, Bas Wouters, Martin Balastik, Clara Shapiro-Koss, Hong Zhang, Annalisa DiRuscio, Hanna S. Radomska, Alexander K. Ebralidze, Giovanni Amabile, Min Ye, Junyan Zhang, Irene Lowers, Roberto Avellino, Ari Melnick, Maria E. Figueroa, Peter J.M. Valk, Ruud Delwel, Daniel G. Tenen
Journal: Journal of Clinical Investigation (2012)

C/EBPs are a family of transcription factors that regulate growth control and differentiation of various tissues. We found that C/EBPγ is highly upregulated in a subset of acute myeloid leukemia (AML) samples characterized by C/EBPα hypermethylation/silencing. Similarly, C/EBPγ was upregulated in murine hematopoietic stem/progenitor cells lacking C/EBPα, as C/EBPα mediates C/EBPγ suppression. Studies in myeloid cells demonstrated that CEBPG overexpression blocked neutrophilic differentiation. Further, downregulation of Cebpg in murine Cebpa-deficient stem/progenitor cells or in human CEBPA-silenced AML samples restored granulocytic differentiation. In addition, treatment of these leukemias with demethylating agents restored the C/EBPα-C/EBPγ balance and upregulated the expression of myeloid differentiation markers. Our results indicate that C/EBPγ mediates the myeloid differentiation arrest induced by C/EBPα deficiency and that targeting the C/EBPα-C/EBPγ axis rescues neutrophilic differentiation in this unique subset of AMLs.
Volkmann's Ischemic Contracture
Authors: Joseph K. Surls
Journal: JAMA (1963)

To the Editor:  —Cases of Volkmann's ischemic contracture are still too common, judging from the frequency with which they are described in the literature. I had occasion recently to review the subject, and I believe that T. D. Brower, writing in the April, 1960, issue of Surgical Clinics of North America correctly emphasizes the frequency when he says, The medical literature in all languages has recorded innumerable cases of Volkmann's ischemic paralysis. Perhaps it would be worth while if a concerted effort were made by the medical journals to highlight Volkmann's ischemic contracture and so erase it from the list of human ills. Such might be accomplished by (1) immediate diagnosis and (2) immediate manual extension, with retention by a plaster splint.
LATE CARDIAC ABNORMALITIES IN ADULT SURVIVORS OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA: A CARDIAC MRI STUDY
Authors: Dipti Gupta, Frank Evans, Jyoti Malhotra, Jennifer Wright, Sharon Reimold, Chaya S. Moskowitz, Joanne F. Chou, Emily Tonorezos, Beverly Huet, Debra A. Eshelman-Kent, Naomi Winick, Richard Steingart, Kevin Oeffinger, Jennifer liu
Journal: Journal of the American College of Cardiology (2014)
STUDIES ON THE INTERRELATIONSHIP BETWEEN THE BLOOD-BRAIN BARRIER AND ENTRY OF VIRUSES INTO THE CENTRAL NERVOUS SYSTEM
Authors: Margret I. Sellers, John F. Lavender
Journal: The Journal of Experimental Medicine (1962)

Inhalation of elevated concentrations of CO2 produces a significant increase in the susceptibility of mice to intravenously inoculated Type II poliovirus. The CO2 effect is directly proportional to the concentration; 2.5 minutes inhalation of a mixture of 30 per cent CO2-70 per cent O2 produces maximal effects, while lower concentrations of CO2 require correspondingly longer periods. The threshold level is 7 per cent; inhalation of lower concentrations, even for long periods of time, fails to enhance virus infectivity. Placing the animals in the CO2 atmosphere before injection of virus does not influence susceptibility; virus must be in the circulation at the time CO2 is inhaled if enhancement of infectivity is to be elicited. The effect is completely reversible, disappearing almost immediately upon withdrawal of the animals from the CO2 atmosphere. CO2 mediates an increase in the entry of virus into the CNS from the circulation but does not affect the spread of virus within the CNS; susceptibility of mice to intracerebrally inoculated poliovirus is not influenced by CO2 inhalation. The mechanism(s) of action of CO2 can be explained, in part, by the dilatation of cerebral blood vessels and increased rate of blood flow through the CNS produced by the CO2. However, other factors, which remain unidentified, contribute to the net effect of CO2. The relationship between the mechanism of action of CO2 and the provoking effects of trauma and violent exercise in poliomyelitis is discussed. Also, a relationship between the CO2 tension of the blood and environmental temperatures on poliovirus susceptibility is proposed.
THE HOST CELL RESPONSE IN THE LOCAL GRAFT-<i>VERSUS</i>-HOST REACTION INDUCED IN THE KIDNEYS OF F1 RATS BY PARENTAL THORACIC DUCT LYMPHOCYTES
Authors: Alvin Volkman
Journal: The Journal of Experimental Medicine (1972)

Radioautographs of infiltrative cells in the kidneys of (Lewis x BN)F(1) rats labeled with tritiated thymidine (TdR(3)H) before the subcapsular injection of parental (Lewis) thoracic duct lymphocytes (TDL) showed a predominantly host-proliferative response by 4 days after grafting. The immediate renal incorporation of TdR(3)H was used to measure the local graft-vs.-host (GVH) reactions. Substantial reactions could still be induced in the face of the considerable degree of leukopenia after 400 R whole body gamma-irradiation. These results suggest that radioresistant cells are capable of carrying on the appropriate host activities and that the weakness of GVH reactions induced after higher doses of irradiation may be due to impairment of the mitotic mechanism of host cells. The importance of circulating leukocytes as a source of immunogenic stimulation was nevertheless substantiated by inducing local GVH reactions with Lew TDL in chimeric parental-type rats that had been repopulated with F(1) bone marrow. This result also emphasizes the nonspecific nature of tissue destruction in the renal GVH reaction in confirmation of Elkins. In this and other situations in which B cells were the predominant F(1) type elements available for interaction with parental-type TDL the reactions were nearly equivalent or equivalent to those in the appropriate controls. Typical local GVH reactions could be induced in heavily irradiated hosts by an inoculum of combined parental and F(1)-type TDL in the apparent absence of mononuclear phagocytes. The possible relationship between the activation of host lymphocytes, the involvement of B cells, and the nonspecific nature of tissue damage in the renal GVH is discussed.
Early Assessment of Proliferation by the Genomic Grade Index (GGI) Predicts Response to Neo-Adjuvant Letrozole.
Authors: S. Singhal, P. Bedard, M. Ignatiadis, B. Haibe-Kains, C. Desmedt, S. Loi, D. Evans, J. Dixon, W. Miller, C. Sotiriou
Journal: Cancer Research (2009)

Abstract Background: Expression of the proliferation antigen Ki-67 after short-term pre-surgical endocrine treatment is predictive of long-term relapse free survival in post-menopausal women with estrogen-receptor (ER) positive breast cancer (Dowsett et al., JNCI 2007). There are no established predictive markers of clinical response to neo-adjuvant endocrine therapy.Methods: Whole genome expression profiles (Affymetrix HG-U133A) from paired tumor biopsies before and after 10 to 14 days of neo-adjuvant letrozole were compared to tumor volume changes over 3 months of treatment for 52 post-menopausal women with hormone receptor positive breast cancer to evaluate early predictive markers of clinical response.Results: Clinical response was observed in 80% Luminal A (24/30) and 59% Luminal B (13/22) tumors (p=0.1). Baseline tumor proliferation assessed by GGI or Ki-67 mRNA expression were not predictive of clinical response (p=0.29 and p=0.73 respectively). The absolute value of GGI at Day 10 to 14 was predictive of clinical response (p=0.001), particularly for luminal B (p=0.001) but not luminal A (p=0.35) tumors. The change in GGI from baseline to Day 10 to 14 was marginally predictive of response (p=0.063). Absolute day 10 to 14 Ki67 mRNA expression and the change in Ki67 mRNA were not associated with clinical response (p=0.54 and p=0.58 respectively). Baseline, absolute Day 10 to 14, and change in the expression of the ER gene (ESR1) or an integrative gene module reflecting ER signaling were not predictive of clinical response.Conclusion: Expression of GGI after 10 to 14 days of neo-adjuvant letrozole and the change in GGI with short-term treatment are predictive of clinical response observed after 3 months of therapy. Early assessment of GGI may be useful to determine which post-menopausal patients with highly-proliferative ER-positive disease benefit from endocrine therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2016.
Topoisomerase IIα Gene Amplification Predicts Favorable Treatment Response to Tailored and Dose-Escalated Anthracycline-Based Adjuvant Chemotherapy in <i>HER-2/neu</i>–Amplified Breast Cancer: Scandinavian Breast Group Trial 9401
Authors: Minna Tanner, Jorma Isola, Tom Wiklund, Björn Erikstein, Pirkko Kellokumpu-Lehtinen, Per Malmström, Nils Wilking, Jonas Nilsson, Jonas Bergh
Journal: Journal of Clinical Oncology (2006)

Amplification of the HER-2/neu and topoisomerase IIalpha (TOP2A) genes has been linked to the effects of anthracyclines. Their role in predicting the outcome of anthracycline-based adjuvant chemotherapy for breast cancer patients has remained controversial.The present substudy of the Scandinavian Breast Group trial 9401, in which an epirubicin-based regimen (nine courses of tailored and dose-escalated fluorouracil, epirubicin, and cyclophosphamide [FEC]) was compared with three or four courses of standard FEC followed by bone marrow-supported high-dose chemotherapy (cyclophosphamide, thiotepa, and carboplatin), included high-risk breast cancer patients (with eight or more positive axillary lymph nodes or at least five nodes with additional poor prognostic indicators). Amplification of HER-2/neu was determined retrospectively in paraffin-embedded tumor tissue sections by chromogenic in situ hybridization. TOP2A was tested only in HER-2/neu-amplified tumors.HER-2/neu amplification alone, which was present in 32.7% of the tumors, was a strong prognostic factor for short relapse-free (P = .0034) and overall survival (P = .0008) but showed no direct association with treatment assignment. TOP2A coamplification, which was present in 37% of HER-2/neu-amplified tumors, was associated with better relapse-free survival in patients treated with tailored and dose-escalated FEC (hazard ratio [HR] = 0.45; P = .049). A statistical multivariate Cox's regression analysis confirmed the predictive significance of TOP2A coamplification (HR = 0.30; P = .020) in HER-2/neu-amplified tumors. There was no such association in patients with HER-2/neu-amplified tumors without TOP2A gene amplification.Coamplification of HER-2/neu and TOP2A may define a subgroup of high-risk breast cancer patients who benefit from individually tailored and dose-escalated adjuvant anthracyclines.
When ignorance is not bliss
Authors: W. Jones
Journal: BMJ (2003)

My naive journey into the world of prescription drugs and their side effects began one chilly October morning 14 years ago, hand in hand with my life changing, soul crushing companion—psoriatic arthritis. I awoke suddenly to find that, out of the blue, my right knee had swollen to the size of a tennis ball. That's strange, I thought to myself; I don't recall having had any bumps or injuries there.

After two weeks, the painful swelling was still causing difficulty in walking, and I went to see my general practitioner. I was referred to an orthopaedic consultant, but it was a nine month wait before I saw him. In his opinion, I had torn a cartilage. However, after another year of tests—during which time another three joints were …
Prophylactic Antibiotics and Prosthetic Joints
Authors: Larry J. Peterson
Journal: JAMA (1980)

<h3>To the Editor.—</h3> As new indications for therapeutic and prophylactic antibiotics are proposed, it is essential that they be carefully examined for validity. Lattimer et al (242:2213, 1979) propose that prophylactic antibiotic therapy be administered to prevent hematogenous spread of infection to prosthetic joints when performing procedures that cause a bacteremia. An infected prosthetic joint is associated with great morbidity and expense. Whether hematogenous spread occurs was debated for several years, but it is now clear that it does.<sup>1</sup>It is seen in asymptomatic patients whose prosthetic joints have been in place for at least 1 1/2 to two years. I have reviewed the literature since 1975 and have found 87 cases of probable hematogenous prosthetic joint infection. I looked particularly at the source and the identity of the bacteria. When the source of the infection was identified (52 cases), it was always from an established infection elsewhere in