tbuckley/cabot-search huggingface dataset:
Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes. U.S. Study Group of Insulin Glargine in Type 1 Diabetes.
Authors: R E Ratner, I B Hirsch, J L Neifing, S K Garg, T E Mecca, C A Wilson
Journal: Diabetes Care (2000)

OBJECTIVE: Insulin glargine (21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin) is a biosynthetic insulin analog with a prolonged duration of action compared with NPH human insulin. This study compared insulin glargine with NPH human insulin in subjects with type 1 diabetes who had been previously treated with multiple daily injections of NPH insulin and regular insulin. RESEARCH DESIGN AND METHODS: This study was a multicenter randomized parallel-group study in which subjects were randomized to receive premeal regular insulin and either insulin glargine (at bedtime) or NPH insulin (at bedtime for patients on once-daily therapy and at bedtime and in the morning for patients on twice-daily therapy) for up to 28 weeks. Dose titration of both basal insulins was based on capillary fasting whole blood glucose (FBG) levels; the goal was a premeal blood glucose concentration of 4.4-6.7 mmol/l. RESULTS: A total of 534 well-controlled type 1 diabetic subjects (mean GHb 7.7%, mean fasting plasma glucose [FPG] 11.8 mmo/l) were treated. A small decrease in GHb levels was noted with both insulin glargine (-0.16%) and NPH insulin (-0.21%; P &amp;gt; 0.05). Significant reductions in median FPG levels from baseline (-1.67 vs. -0.33 mmol/l with NPH insulin, P = 0.0145) and a trend for a reduction in capillary FBG levels were achieved with insulin glargine. After the 1-month titration phase, significantly fewer subjects receiving insulin glargine experienced symptomatic hypoglycemia (39.9 vs. 49.2%, P = 0.0219) or nocturnal hypoglycemia (18.2 vs. 27.1%, P = 0.0116) with a blood glucose level &amp;lt;2.0 mmol/l compared with subjects receiving NPH insulin. CONCLUSIONS: Lower FPG levels with fewer episodes of hypoglycemia were achieved with insulin glargine compared with once- or twice-daily NPH insulin as part of a basal-bolus regimen in patients with type 1 diabetes.
Medical Researchers and the Media
Authors: Michael S. Wilkes, Richard L. Kravitz
Journal: JAMA (1992)

<h3>Objective.</h3> —To study the experience of recently published authors with the news media. <h3>Design.</h3> —A self-administered questionnaire. <h3>Participants.</h3> —All first authors of scientific articles published in<i>JAMA and The New England Journal of Medicine</i>during a 6-month period. Of 397 surveyed, 92% responded. <h3>Main Outcome Measures.</h3> —Researchers were asked about (1) their experience with the news media, (2) their attitudes toward the dissemination of health-related research to the general public, and (3) their attitudes toward the lay press. <h3>Results.</h3> —Of respondents, 65% stated that their research was discussed in the lay press, and 60% reported that they were directly contacted by the press. Researchers had positive attitudes toward the press; 86% reported that news reports based on their research were accurate and 44% felt that media coverage would help them achieve their overall professional goals. Positive aspects of media coverage most frequently endorsed were that (1) it improves the image of the profession, (2) it informs the professional community of their research, and (3) it allows the public to understand the topic better. Negative aspects of media coverage were (1)it gives the impression that the researcher is seeking publicity, (2) it creates jealousy among colleagues, and (3) it takes too much time. Researchers were not eager to change the existing dissemination process, yet they endorsed the need for uniform standards concerning relations with the press. <h3>Conclusions.</h3> —The majority of first authors in two leading medical journals reported substantial media coverage of their research, expressed generally positive sentiments about the press coverage of their work, and expressed a need for consensus on interactions involving the press. (<i>JAMA</i>. 1992;268:999-1003)
Fatal Lymphohistiocytic Proliferation Owing to Epstein-Barr Virus-Reply
Authors: Gabriel Cividalli
Journal: JAMA (1982)

In Reply.—  Drs Purtilo and Johnson suggest that EBV infection in an immune deficient XX/XY chimeric host could have led to the fatal lymphohistiocytic proliferation in our patient, analogous, perhaps, to the XLP. They base their suggestion on the high incidence of XX/XY chimerism in marmosets, which are also susceptible to EBV-induced lymphoproliferative disease. While this possibility is intriguing, there is no anamnestic or laboratory indication of a previous immune deficiency or EBV infection in our patient. The titer of anti-EBV-VCA antibodies, tested twice in the initial phase of the disease, IgG 1:128 and IgA negative, did not indicate a recent EBV infection. Nevertheless, we gratefully accept the suggestion of Drs Purtilo and Johnson to probe for the virus in tissues with the new techniques mentioned in their letter.
The Origin and Treatment of Schizophrenic Disorders
Authors: Sanford Meyerowitz
Journal: JAMA (1974)

Because of the lack of conceptual clarity about schizophrenia, both the search for causes and the development of methods for treatment have posed a continuing challenge for psychiatry. This succinct, well-written volume based on the author's 1967 Salmon Lectures addresses itself successfully to both aspects of the challenge through a focused rather than comprehensive approach. Citing his own investigations and the work of others, the author defines and illustrates the nature of the disordered family settings in which the illness develops. Starting with an examination of the role of the family in the development of the child, he proceeds to a careful description and categorization of the intrafamilial circumstances that affect the growing child who will be vulnerable to schizophrenia. He illustrates the changes that occur in these disordered families and the developmental crises for the patient that precede the emergence of the first acute psychotic episode. In discussing the
Is Gastric Carcinoma an Infectious Disease?
Authors: Pelayo Correa
Journal: New England Journal of Medicine (1991)

Two articles in this issue of the Journal reach the conclusion that past infection with Helicobacter pylori increases considerably the risk of gastric carcinoma.1 , 2 One reaction to this interesting finding could be a desire to eradicate H. pylori as a cancer-prevention measure, although the task would be extremely difficult, since the great majority of the subjects in these studies who did not have cancer were infected with the same bacteria (76 percent in Hawaii and 60 percent in California).The difficulty of interpreting the messages of these two studies, and the potential for misinterpretation, may be aggravated by the meager . . .
Recombinant interleukin 7, pre-B cell growth factor, has costimulatory activity on purified mature T cells.
Authors: P J Morrissey, R G Goodwin, R P Nordan, D Anderson, K H Grabstein, D Cosman, J Sims, S Lupton, B Acres, S G Reed
Journal: The Journal of Experimental Medicine (1989)

The activation of highly purified murine peripheral T cells in vitro by Con A is dependent on a co-stimulatory signal that is not IL-1 or IL-2. Previous evidence has demonstrated that the recently defined lymphokine IL-6 could provide costimulatory activity for purified T cells cultured with Con A. In this report we demonstrate that IL-7 also has potent co-stimulatory activity for purified murine T cells, as well as its previously described ability to support the growth of pre-B cells in Witte-Whitlock cultures. When rIL-7 was added to cultures of purified T cells together with Con A, it induced the expression of IL-2 receptors, IL-2 production, and consequently proliferation. In addition, IL-7 exhibited the same magnitude of activity in this assay as IL-6. Also, anti-IL-6 antibody which inhibited the IL-6-induced response had no effect on the IL-7 response. Thus, IL-7 does not act by inducing IL-6. These results demonstrate that IL-7, a potent growth stimulus for pre-B cells, also has a role in T cell activation.
More patients are getting rapid access to carotid endarterectomy, but variation remains
Authors: Z. Kmietowicz
Journal: BMJ (2013)

<h3>Objective</h3> To prepare a history of the enactment of California Assembly Bill 13 (AB 13), a state law prohibiting smoking in most workplaces passed in 1994, and to discuss its initial impacts. <h3>Methods</h3> Data were gathered from open ended interviews with representatives of voluntary health organisations, local government organisations, and principal legislators involved in the process, as well as observers around the state who could provide insight into the legislative process. Information was also obtained from legislative hearings and debates, public documents, letters and personal communications, internal memoranda, and news reports. <h3>Results</h3> The success of local tobacco control legislation in California led to a situation in which some health groups were willing to accept state preemption in order to attract the support of the state restaurant association for a bill. The decision to accept this preemption compromise was made by the state level offices of the voluntary health agencies without consulting the broader tobacco control community within California. In contrast, local tobacco control advocates did not accept this compromise, in part because of their belief that local legislation was a better device to educate the public, generate media coverage, and build community support for enforcement and implementation of clean indoor air and other tobacco control laws. Enactment of AB 13 was associated with a slowing of all local tobacco control legislation, including youth oriented laws. <h3>Conclusions</h3> Because its supporters initially doubted that AB 13 would pass, there was never an effort to reconcile the policy differences between state oriented and locally oriented tobacco control policies. This lack of consensus, combined with the political realities inherent in passing any state legislation, led to a bill with ambiguous preemption language which replaced the “patchwork of local laws” with a “patchwork of local enforcement.”
Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease.
Authors: A. M. Schols, W. A. Buurman, A. J. Staal van den Brekel, M. A. Dentener, E. F. Wouters
Journal: Thorax (1996)

BACKGROUND: An increase in resting energy expenditure (REE) commonly occurs in patients with chronic obstructive pulmonary disease (COPD), the cause of which is as yet unknown. The objective of this study was to assess the relationship between REE, acute phase proteins, and inflammatory mediators in patients with COPD. METHODS: Thirty patients were studied and 26 healthy age-matched subjects served as controls. REE was measured by indirect calorimetry and adjusted for fat-free mass (FFM) by bioelectrical impedance analysis. Tumour necrosis factor alpha (TNF-alpha), soluble tumour necrosis receptor (sTNF-R)55 and sTNF-R75, interleukin (IL)-6, IL-8, and lipopolysaccharide binding protein (LBP) were measured by ELISA. RESULTS: Fourteen patients had a normal REE and in 16 it was raised. The mean body mass index and fat mass were significantly lower in the latter but pulmonary function data were similar in the two groups. In the 30 patients with COPD the mean (SD) sTNF-R75 was 1.7 (1.0) ng/ml compared with 1.1 (0.4) ng/ml in the controls; C-reactive protein (CRP) was detectable (&gt; 5 micrograms/ml) in eight patients compared with none of the control subjects, and LBP was 13.2 (7.7) micrograms/ml compared with 8.6 (3.1) micrograms/ml in the controls. The patients with a raised REE had increased mean levels of CRP compared with the patients with a normal REE (median 5.5 micrograms/ml (range 5-193) and &lt; 5 micrograms/ml, respectively); the same was true for LBP (median 12.4 micrograms/ml (range 8.1-39.1) and 9.5 micrograms/ml (range 5.0-16.6), respectively), but sTNF-R55 and R75 and IL-8 were similar in the two groups. Of the 16 patients with a raised REE, the CRP level was increased in eight and normal in eight. In those with an increased level of CRP the FFM was decreased and LBP, IL-8, and sTNF-R55 and R75 were increased compared with those with normal CRP levels. CONCLUSIONS: A subset of patients with COPD with an increased REE and decreased FFM have increased levels of acute phase reactant proteins and inflammatory cytokines in their serum; these phenomena may be causally related.
Abstract B25: DNA hypermethylation in prostate cancer is a consequence of aberrant epithelial differentiation and hyperproliferation
Authors: Davide Pellacani, Dimitra Kestoras, Alastair P. Droop, Fiona M. Frame, Paul A. Berry, Mitchell G. Lawrence, Michael J. Stower, Matthew S. Simms, Vincent M. Mann, Anne T. Collins, Gail P. Risbridger, Norman J. Maitland
Journal: Cancer Research (2013)

Abstract Prostate cancer (CaP) is mostly composed of differentiated luminal cells, but contains a small subpopulation of undifferentiated basal cells (including stem-like cells), which is thought to be the driving force of CaP. In cancers, CpG island hypermethylation has been associated with gene downregulation, but the causal relationship between the two phenomena is still debated. This study aimed to understand the function and origin of CpG island hypermethylation in CaP, in the context of cancer hierarchy and differentiation. We have analyzed separately primary prostate basal and luminal cells derived from BPH and CaP. This allowed us to dissect the intra-tumor heterogeneity, and to understand the origin of gene downregulation and hypermethylation in CaP. We report that a set of genes commonly hypermethylated in CaP (including GSTP1) is: (i) downregulated as a result of prostate-specific epithelial differentiation in both CaP and benign prostatic hyperplasia (BPH); (ii) selectively hypermethylated in differentiated (luminal) cancer cells, process promoted by the hyperproliferating phenotype of these cells; (iii) actively expressed and methylation free in undifferentiated (basal) CaP cells. Downregulation and hypermethylation of these genes is not essential for tumor development or tumor expansion. Moreover, for all these genes, downregulation induced by prostate-specific differentiation, is independent of DNA hypermethylation, and is associated with detachment of RNA PolII from their promoter and reduction in histone marks associated with active transcription. Citation Format: Davide Pellacani, Dimitra Kestoras, Alastair P. Droop, Fiona M. Frame, Paul A. Berry, Mitchell G. Lawrence, Michael J. Stower, Matthew S. Simms, Vincent M. Mann, Anne T. Collins, Gail P. Risbridger, Norman J. Maitland. DNA hypermethylation in prostate cancer is a consequence of aberrant epithelial differentiation and hyperproliferation. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr B25.
APPROVED INTERNSHIPS AND RESIDENCIES IN THE UNITED STATES
Authors: Edward H. Leveroos
Journal: JAMA (1949)

ANNUAL REPORT ON INTERNSHIPS AND RESIDENCIES BY THE COUNCIL ON MEDICAL EDUCATION AND HOSPITALS OF THE AMERICAN MEDICAL ASSOCIATION  The approved internship and residency lists are again being published in a special Internship and Residency Number ofThe Journal. They include changes in and additions to the lists as of May 1, 1949. Subsequent changes will appear in the Educational Number ofThe Journal, scheduled for publication in September.  The 1949 internship list includes data on all hospitals presently approved by the Council for intern training. Approved hospitals are listed geographically followed by information relating to the type of ownership or control, the bed capacity, number of annual admissions, percentage of service cases, type of internship offered, length of program, number of positions available, affiliated assignments, outpatient service, autopsy rate and monthly stipend. In view of the
Abstract 2445: Estrogen promotes tumorigenesis by ADP-ribosyl-acceptor hydrolase 1 (ARH1)-deficient cells and mice
Authors: Jiro Kato, Xiangning Bu, Joel Moss
Journal: Cancer Research (2014)

Abstract ADP-ribosylation, a post-translational modification in which the ADP-ribose of NAD is transferred to specific acceptors, is used by bacterial toxins to disrupt host cell biosynthetic, regulatory and metabolic pathways. Mammalian cells also use ADP-ribosylation reactions to regulate protein activity. The content of ADP-ribosylated acceptors is tightly regulated by enzymes that transfer ADP-ribose to acceptors i.e., ADP-ribosyltransferases (ARTs), and those that cleave the ADP-ribose acceptor bond, i.e., ADP-ribose-acceptor hydrolases (e.g., ARHs). ADP-ribosyl-acceptor hydrolase 1 (ARH1) is responsible for the hydrolysis of the α-ADP-ribosylarginine(protein) bond. We reported previously that ARH1-deficient mouse embryonic fibroblasts (MEFs) had greater proliferation rates, and formed more colonies in soft agar and tumors in nude mice than their wild-type (WT) counterparts. Consistent with these results with MEFs, ARH1-deficient (ARH1-/-) and heterozygous (ARH1+/-) mice developed tumors more frequently than their WT counterparts (Kato et al, 2011 Cancer Res.). Furthermore, the ARH1 gene from tumors isolated from ARH1+/- MEFs, and from tumors isolated from ARH1+/- mice contained mutations that affected function. Because loss of the functioning allele in ARH1+/- MEFs and mice resulted in tumorigenesis, we infer that ARH1 is a tumor suppressor gene. Female ARH1-/- and ARH1+/- mice developed tumors and metastasis more frequently than male mice (e.g., adenocarcinomas, lymphomas), and developed tumors at a younger age than male mice. Consistent with the gender effect on incidence of tumors in ARH1-/- mice, tumor growth by ARH1-/- MEFs injected subcutaneously in an “estrogen group” (i.e., female, female ovariectomized [FO] supplemented with 17-β-estradiol [E2], male supplemented with E2) of nude mice was significantly faster than that seen in a “non-estrogen group” (i.e., male, FO) of mice. Pulmonary metastasis following intravenous injection of ARH1-/- MEFs in an “estrogen group” of nude mice were larger in size than those in a “non-estrogen group”. Further, estrogen promoted the survival of ARH1-/- MEFs in the circulation and thus enhanced metastatic potential. Our data demonstrate that control of protein-ADP-ribosylation by ARH1 is important for cell proliferation and tumorigenesis. Estrogen enhanced pulmonary metastasis, tumor growth and survival of circulating tumor cells. Funding: Intramural Research Program, NIH, NHLBI. Citation Format: Jiro Kato, Xiangning Bu, Joel Moss. Estrogen promotes tumorigenesis by ADP-ribosyl-acceptor hydrolase 1 (ARH1)-deficient cells and mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2445. doi:10.1158/1538-7445.AM2014-2445
ER/PR positive epidermotropic primary cutaneous eccrine carcinoma as a cutaneous manifestation of MEN 2B
Authors: Phyu P. Aung, Leomar Y. Ballester, Zied Abdullaev, Svetlana D. Pack, Deborah L. Cummins, Meera Mahalingam
Journal: Journal of the American Academy of Dermatology (2013)
Autism spectrum disorder is not as certain as implied
Authors: D. Simpson
Journal: BMJ (2003)

EDITOR—Szatmari's editorial implies more certainty about the existence of an autism spectrum and causes of autism than is warranted.1 Debate remains about the validity and usefulness of a broad definition of autism.2

Autism and Asperger's syndrome are distinct, and although they share common difficulties in social relatedness and obsessiveness, they can be distinguished …
1018-144 Assessment of coronary atherosclerotic plaque composition by multidetector computed tomography: Comparison to intravascular ultrasound
Authors: Stephan Achenbach, Fabian Moselewski, Dieter Ropers, Karsten Pohle, Udo Hoffmann, Maros Ferenick, Suhny Abbara, Ricardo Cury, Ray Chan, Ik-kyung Jang, Tom Brady, Werner G Daniel
Journal: Journal of the American College of Cardiology (2004)
Staurosporine: A Prototype of a Novel Class of Inhibitors of Tumor Cell Invasion?
Authors: Catherine A. O'Brian, Nancy E. Ward
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Staurosporine: A Prototype of a Novel Class of Inhibitors of Tumor Cell Invasion? Get access Catherine A. O'Brian, Catherine A. O'Brian Search for other works by this author on: Oxford Academic PubMed Google Scholar Nancy E. Ward Nancy E. Ward Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 22, 21 November 1990, Pages 1734–1735, https://doi.org/10.1093/jnci/82.22.1734 Published: 21 November 1990 Article history Received: 15 October 1990 Accepted: 16 October 1990 Published: 21 November 1990
Orthopaedic departments will have more difficulty meeting 18 week waiting target
Authors: Michael Day
Journal: BMJ (2007)

Experts have highlighted considerable hurdles facing the NHS as it prepares to meet the government's 2008 deadline for eliminating waiting times of more than 18 weeks.

Last month, the then health minister Andy Burnham said that long delays between referral by a GP and hospital treatment would be banished for good, with no one waiting more than 18 weeks, by December next year.

He said, “This is in my view the end of waiting. I think this represents the culmination of our 10 year programme.”

At a meeting of clinicians and Department of Health civil servants last week, however, warnings were sounded …
Gastrointestinal Manifestations of Common Variable Immunodeficiency Diagnosed by Video- and Capsule Endoscopy
Authors: E. Mihály, A. Németh, T. Zágoni, A. Német, K. Werling, I. Rácz, Z. Tulassay
Journal: Endoscopy (2005)

The discovery of multiple gastrointestinal polyps during endoscopy indicates the presence of an inherited polyposis syndrome, but this finding can also be associated with noninherited polyposis syndromes, such as nodular lymphoid hyperplasia. Although nodular lymphoid hyperplasia can occur in the absence of immunodeficiency, it can be a manifestation of common variable immunodeficiency. Common variable immunodeficiency is a syndrome which is characterized by immature B lymphocytes that recognize antigens and proliferate in response to an antigen challenge, but which then fail to differentiate to become immunoglobulin-secreting plasma cells [1]. Possible factors suspected of causing this condition include an intrinsic abnormality of B lymphocytes, and dysfunction of T helper cells or of complement components. This abortive differentiation pattern leads to panhypogammaglobulinemia, recurrent sinopulmonary inflammation, splenomegaly, and intestinal lymphoid hyperplasia [2]. Because malignant tumors, such as lymphoma or stomach cancer, can develop in association with common variable immunodeficiency, annual surveillance of these patients is necessary [3]. We present a patient with gastrointestinal manifestations of common variable immunodeficiency.