tbuckley/cabot-search huggingface dataset:
Community-Associated MRSA — Resistance and Virulence Converge
Authors: Henry F. Chambers
Journal: New England Journal of Medicine (2005)

Laypeople and health care professionals alike recognize Staphylococcus aureus as an important cause of disease and understand that antibiotic-resistant strains pose a threat to the community. Before the availability of antibiotics, invasive staphylococcal disease was often fatal, and the introduction of penicillin in the 1940s dramatically improved survival. Although penicillinase-producing strains soon emerged, methicillin and other penicillinase-stable β-lactam agents filled the breach. However, methicillin-resistant strains of S. aureus (MRSA), which are resistant to the entire class of β-lactam agents, were identified almost immediately and are now found in hospitals worldwide. Despite the growing prevalence of MRSA in hospitals, these strains . . .
Staff Attitudes and Conflict Regarding the Use of Methadone in the Treatment of Heroin Addiction
Authors: BARRY S. BROWN, DONALD R. JANSEN, URBANE F. BASS
Journal: American Journal of Psychiatry (1974)

Realizing that attitudes toward drug use held by staff members of methadone maintenance clinics have a strong influence on the treatment given, the authors sampled the opinions of ex-addict counselors maintained with methadone, ex-addict counselors who were abstinent, nonaddict counselors, and administrative and supervisory staff. The staff uniformly viewed methadone maintenance as preferable to the use of heroin but as significantly less desirable than the person's functioning without drugs. The implications of these attitudes for treatment are discussed.
Vitamin D Levels In Children With Eosinophilic Esophagitis and Gastroesophageal Reflux
Authors: K. Waterhouse, A. Katta, J. Teckman, T. Foy, J. Derdoy, A. Jain, A. Knutsen, B. Becker
Journal: Journal of Allergy and Clinical Immunology (2011)
Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation: no causal relation with diabetic autonomic neuropathy.
Authors: R E Ryder, D R Owens, T M Hayes, M A Ghatei, S R Bloom
Journal: BMJ (1990)

OBJECTIVE--To examine the traditional view that unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation in insulin dependent diabetes mellitus are manifestations of autonomic neuropathy. DESIGN--Perspective assessment of unawareness of hypoglycaemia and detailed assessment of autonomic neuropathy in patients with insulin dependent diabetes according to the adequacy of their hypoglycaemic counterregulation. SETTING--One routine diabetic unit in a university teaching hospital. PATIENTS--23 Patients aged 21-52 with insulin dependent diabetes mellitus (seven with symptoms suggesting autonomic neuropathy, nine with a serious clinical problem with hypoglycaemia, and seven without symptoms of autonomic neuropathy and without problems with hypoglycaemia) and 10 controls with a similar age distribution, without a personal or family history of diabetes. MAIN OUTCOME MEASURES--Presence of autonomic neuropathy as assessed with a test of the longest sympathetic fibres (acetylcholine sweatspot test), a pupil test, and a battery of seven cardiovascular autonomic function tests; adequacy of hypoglycaemic glucose counterregulation during a 40 mU/kg/h insulin infusion test; history of unawareness of hypoglycaemia; and response of plasma pancreatic polypeptide during hypoglycaemia, which depends on an intact and responding autonomic innervation of the pancreas. RESULTS--There was little evidence of autonomic neuropathy in either the 12 diabetic patients with a history of unawareness of hypoglycaemia or the seven patients with inadequate hypoglycaemic counterregulation. By contrast, in all seven patients with clear evidence of autonomic neuropathy there was no history of unawareness of hypoglycaemia and in six out of seven there was adequate hypoglycaemic counterregulation. Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation were significantly associated (p less than 0.01). The response of plasma pancreatic polypeptide in the diabetic patients with adequate counterregulation but without autonomic neuropathy was not significantly different from that of the controls (change in plasma pancreatic polypeptide 226.8 v 414 pmol/l). The patients with autonomic neuropathy had a negligible plasma pancreatic polypeptide response (3.7 pmol/l), but this response was also blunted in the patients with inadequate hypoglycaemic counterregulation (72.4 pmol/l) compared with that of the controls (p less than 0.05). CONCLUSIONS--Unawareness of hypoglycaemia and inadequate glucose counterregulation during hypoglycaemia are related to each other but are not due to autonomic neuropathy. The blunted plasma pancreatic polypeptide responses of the patients with inadequate hypoglycaemic counterregulation may reflect diminished autonomic activity consequent upon reduced responsiveness of a central glucoregulatory centre, rather than classical autonomic neuropathy.
Abstract C38: Whole-genome sequencing of paired androgen-dependent and -independent prostate cancer cell lines: Potential role of novel targets in PI3K and Notch signaling pathways in resistance to hormonal therapy
Authors: Gillian L. Dalgliesh, Joanne L. Hartley, Cary H. O'Donnell, James R. Bradford, Iain McKendrick, Barry R. Davies
Journal: Cancer Research (2012)

Abstract The growth of the majority of prostate tumors is driven by androgens signaling through the androgen receptor. Most patients initially respond to androgen deprivation therapies such as LHRH analogues and anti-androgens like bicalutamide, but after a varying duration of treatment, patients generally develop resistance to these therapies and their tumor progresses to an androgen independent state. Molecular mechanisms that drive androgen independent disease include mutation and amplification of androgen receptor (AR), androgen-independent activation of AR, and AR-independent mechanisms. The aim of this project was to sequence the entire genome of pairs of cell lines, modeling the progression to androgen independent disease, to increase our understanding of these mechanisms and identify new therapeutic targets. Four ‘parental’ prostate cancer cell lines, all of which are sensitive to hormone deprivation, and an androgen independent derivative of each line, derived either by culturing in bicalutamide or growing in the absence of androgens, were subjected to whole genome sequencing. Genomic variants present in the androgen independent but not the parental lines, presumed to be acquired during the progression to androgen independence, were then identified. To find any commonality between the four different pairings, the derived variants were then mapped to functional biological pathways and their likely impact on protein function predicted. Interestingly, derived mutations in the PI3K and Notch signaling pathways were identified in multiple cell lines. In addition to the analysis of derived mutations, baseline characterization of genomic rearrangements and copy number changes in cell lines highlighted variability in the patterns and prevalence of these events as well as uncovering aberrations in genes known to impact prostate cancer development (PTEN, AR, TMPRSS2 rearrangement). This extensive genome sequencing effort has yielded a deeper understanding of potential pathways and molecular events that occur during the acquisition of resistance to anti-androgen therapy, using in vitro models of prostate cancer. These candidates now require validation in tissue samples from prostate cancer patients and functional assays. Citation Format: Gillian L. Dalgliesh, Joanne L. Hartley, Cary H. O'Donnell, James R. Bradford, Iain McKendrick, Barry R. Davies. Whole-genome sequencing of paired androgen-dependent and -independent prostate cancer cell lines: Potential role of novel targets in PI3K and Notch signaling pathways in resistance to hormonal therapy [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C38.
ON ONE OF THE CURABLE FORMS OF DEAFNESS
Authors: T. Westropp
Journal: BMJ (1855)

3rah of the Provincial Medical and 8urgical ciation, -a Ah meeting held on the 3rd of May.It Wa aeomm- pied by a seres of observations, in reference specially to t opeation of excision of the knee; but as those observa- tions wr arranged mainly with the view of placing before my audience the present state of our experience on the question, in order to elicit discussion, and as 1 am prepaing a memoir upon the subject of the operation in all its bear- ins, I have contented myself, on the present occasion, with simply placing on record the case, together with a few com- ments on its more prominent features.Asuredly, one of the most remarkable circumstances connected with the operation, is the entire absence of shock.There were never present any symptoms of such a condi- tion.I believe most fully that the constitutional disturb- ance was diminished by the extirpation of the diseased
Reducing Falls Among Patients in Nursing Homes-Reply
Authors: Wayne A. Ray
Journal: JAMA (1997)

<h3>In Reply</h3> —Dr Cooper's retrospective, observational study is consistent with several reports in the literature that former users of psychotropic drugs with sedative or autonomic effects have lower rates of falls and fractures than do current users.<sup>1</sup>We concur with Drs Bernabei and Carbonin that, because the study unit of randomization was the facility, imbalance between treatment and control facilities with regard to factors that influence risk of falls and injuries was of concern. For this reason, we collected information on falls in the 365 days preceding the study, which provides an integrated measure of how patient characteristics and facility factors that influence risk of falls differed between the study groups. If intervention facilities had more staff, safer environments, or other factors that prevented falls, study residents in these facilities should have had fewer falls in the previous year. As shown in Table 1 of our article, this did not occur.
Language growth after puberty?
Authors: Carlos P. Otero
Journal: Behavioral and Brain Sciences (1996)

Abstract The range of hypotheses considered is surprising in that the most arguably plausible one is not included: the invariant principles of language are available for life, while the parameters of variation cannot be set after puberty. This hypothesis provides a better explanation than the author's for both the deep similarities and the vast differences between child “language growth” and adult language acquisition.
What We Don't Know about Genetic Counseling
Authors: Frederick Hecht, Lewis B. Holmes
Journal: New England Journal of Medicine (1972)

The rush to acquire knowledge in medical genetics means that more information is potentially available for the consumer. How is this information being transmitted? How is it being received? What are its effects?As Leonard, Chase and Childs point out in this issue of the Journal, the evaluation of genetic-counseling technic and the results of genetic counseling "have not been in the mainstream of research...." However regrettable, this is true.The paper by Leonard and her associates provides a particular perspective. Families were evaluated retrospectively by a single interviewer (the senior author, who was at the time a medical student). . . .
Abstract 942: Decreasing the AKT feedback loop with arsenic trioxide enhances mTORi anti-tumor effects.
Authors: Cynthia Guilbert, Matthew G. Annis, Peter Siegel, Wilson H. Miller, Koren K. Mann
Journal: Cancer Research (2013)

Abstract Inhibitors of the mammalian target of rapamycin (mTORi) have exciting clinical activity in renal cell carcinoma, breast cancer, and some hematologic malignancies. However, the potential benefits of mTOR inhibition may be limited by a feedback mechanism that results in AKT activation. While mTORi can block important growth promoting events downstream from TORC1, an increased activation of AKT may inhibit apoptotic signals. Increased AKT activity resulting from mTOR inhibition is a result of increased growth factor/MAPK signaling or alternatively, via the second mTOR complex, TORC2. We have previously shown that arsenic trioxide (ATO) inhibits AKT activity and in some cases, decreases AKT protein expression. Therefore, we propose that combining ATO and mTORi may circumvent the AKT feedback loop and increase the anti-tumor effects of these drugs. Using a panel of breast cancer cell lines, we find that ATO, at clinically achievable doses, can enhance the inhibitory activity of the mTORi temsirolimus in some, but not all, cell lines. MCF-7, MDA-MB-468, and SKBR3, but not T47D cells, exhibit a decrease in cell number that correlates with an increase in the percentage of cells arrested in the G0/G1 phase of the cell cycle. In all these cell lines, temsirolimus treatment resulted in AKT activation, which was decreased by concomitant ATO treatment only in MCF-7, MDA-MB-468, and SKBR3 cell lines. Treatment with mTORi also results in activated ERK signaling, which is decreased with ATO co-treatment in MCF7, MDA-MB-468, and SKBR3. These data indicate that, when effective, ATO decreases phospho-AKT and ERK concomitantly. We next tested the toxicity and efficacy of rapamcyin plus ATO combination therapy in a MDA-MB-468 xenograft model. The combination was well-tolerated, and rapamycin did not increase ATO-induced liver enzyme levels. In contrast, the combination was significantly more effective at inhibiting tumor growth. The increased anti-tumor effects corresponded with ATO decreasing the rapamycin-induced phospho-Akt, phospho-ERK, and phospho-4EBP1 within the tumor. Therefore, we propose that adding ATO to mTORi treatment may overcome the negative feedback loop by decreasing MAPK and activated AKT in addition to the downstream targets of mTOR/TORC1. Citation Format: Cynthia Guilbert, Matthew G. Annis, Peter Siegel, Wilson H. Miller, Koren K. Mann. Decreasing the AKT feedback loop with arsenic trioxide enhances mTORi anti-tumor effects. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 942. doi:10.1158/1538-7445.AM2013-942
'LFTs' Test More Than the Liver
Authors: John H. Helzberg
Journal: JAMA (1986)

Biochemical studies of the liver, known to clinicians as LFTs, can be sensitive to a greater or lesser degree, but they are never specific. The clinician can use them for no more than to infer what is going on in the liver. That is especially true of metastatic liver disease, where it has long been known that, even with diffuse hepatic metastases and after combining laboratory tests with imaging procedures, no more than 75% of metastases can be detected. 1   In this issue ofTHE JOURNAL, Larroquette and coworkers 2 reenforce the view that abnormal findings from hepatic chemistries in patients receiving combination chemotherapy for breast cancer do not necessarily, or usually, signify metastatic disease to the liver. Fifty-nine percent of 190 patients in their retrospective study had abnormal findings from liver chemistries while receiving chemotherapy. Within one year after treatment, however, 90% of those who had developed hepatic enzyme
67 EFFICACY AND SAFETY OF SORAFENIB IN PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC): SUBANALYSIS OF SHARP TRIAL BASED ON BARCELONA CLINIC LIVER CANCER (BCLC) STAGE
Authors: J. Bruix, J.L. Raoul, M. Sherman, M. Shan, G. Lentini, A. Nadel, D. Voliotis, J.M. Llovet
Journal: Journal of Hepatology (2009)
Haploidentical T-cell alpha beta receptor and CD19–depleted stem cell transplant for Wiskott-Aldrich syndrome
Authors: Gaurav Kharya, Zohreh Nademi, T. Ronan Leahy, Janice Dunn, Dawn Barge, Ansgar Schulz, Andrew Cant, Andrew Gennery, Mary Slatter
Journal: Journal of Allergy and Clinical Immunology (2014)
On the utility of an evolutionary approach to infant crying
Authors: Rebecca M. Wood
Journal: Behavioral and Brain Sciences (2004)

Soltis' analysis of signal functions of young infants' cries stimulates testable questions regarding abuse, neglect, and infanticide. Nevertheless, his evolutionary perspective oversimplifies the cry event, and does little to promote developmental analysis of crying during infancy. Studies of the cry in its behavioral and developmental context are needed if we are to understand the proximate causes of optimal and suboptimal care.
Beef safety compromised, says former CMO
Authors: J. Warden
Journal: BMJ (1998)

For five years at the height of Britain's crisis over bovine spongiform encephalopathy (BSE), government assurances that beef was safe to eat were based on a false assumption that abattoir surveillance was being enforced, the official inquiry into BSE was told in London this week.

Sir Kenneth Calman, who was until recently England's chief medical officer and who since 1991 issued at least five public assurances that beef was safe, revealed to the inquiry his concern at being told for the first time in late 1995 that on four occasions spinal cord had been found still attached to bovine carcases at abattoirs, in contravention of the law. This meant that potentially contaminated …
Treatment of Raynaud's phenomenon with ketanserin.
Authors: N H Cox, P A Dufton
Journal: BMJ (1984)

which after convincing recovery can relapse only one week after six weeks' supervised treatment including high dose parenteral thiamine ?3Many ingrained assumptions concerning the prevalence and supposed lack of pathophysiological importance of thiamine deficiency in alcoholics with liver disease predate or ignore the use of functional assays.These assumptions are not all in the interests of patient survival and merit urgent revision.46We look forward to integrated studies incorporating the systematic prolonged use of thiamine in the supraphysiological dosages that functional tests indicate necessary to raise and maintain tissue transketolase activity.Dr Dancy and others did not (as we requested) give any further dietary history of their alcoholic patients.They did make the point (with which we agree) that "any sick alcoholic merits a trial of thiamine... ." Fr the sake of consistency we invite them to clarify whether or not they think their study provides ground for withholding such treat- ment from ill patients with active liver disease and normal or high blood concentrations of thiamine, its esters, or both.
Catnip and the Alteration of Consciousness
Authors: Basil Jackson
Journal: JAMA (1969)

It has been found that<i>Nepeta cataria</i>(catnip) is now being used for its psychedelic effects. No previous mention of the psychopharmacological effects of this drug have been found in the literature. Patients who had been using cataria regularly, experienced effects very similar to those produced by marihuana.
Novel cytomorphology of the giant proerythroblasts of parvovirus B19 infection
Authors: Prasad Rao Koduri
Journal: American Journal of Hematology (1998)

The morphology of the giant proerythroblasts (GPE) in air-dried and Wright-Giemsa-stained smears of bone marrow in 16 patients with pure red cell aplasia (PRCA) caused by parvovirus B19 infection is described. B19 infection was diagnosed by the presence of the virus or viral DNA and/or IgM antibodies. Twelve patients had chronic hemolytic anemia and aplastic crisis and 4 patients had AIDS with chronic PRCA. In patients with chronic hemolytic anemia and aplastic crisis, GPE were not detectable in bone marrow biopsies that showed any degree of recovery of erythropoiesis. The GPE morphology was quite variable. The early (basophilic) GPE measured 25 to 35 microm in diameter, had a narrow rim of intensely blue and often vacuolated cytoplasm with pseudopodia, round nuclei with compact uncondensed chromatin, and an indistinct and inclusion-like purple-colored tinctorial change. The "intermediate" and "late" GPE measured 25 to 45 microm in diameter and showed cytoplasmic swelling, gradual loss of cytoplasmic basophilia, and fraying of the cytoplasm with focal rupture; the nuclei showed an increase in volume, a highly uncondensed and coarse sieve-like chromatin, and 1 to 3 prominent, pale to moderate purple inclusion-like nucleoli or inclusions. Bare nuclei similar in size and chromatin pattern to those of the GPE were present in proximity to the GPE and may have arisen from the GPE by dissolution of the cytoplasm. The glassy intranuclear inclusions with central clearing, the so-called lantern cells described in formalin-fixed tissues of patients with B19 infection, were absent in all cases. These findings suggest that direct toxic cell injury rather than apoptosis may be involved in the pathogenesis of erythroid aplasia in B19 infection.
US cigarette consumption falls to lowest point since 1951
Authors: Roger Dobson
Journal: BMJ (2006)

Sales of cigarettes in the United States are at their lowest point for more than half a century.

Sales have slumped by around 21% since 1998, including a 4.2% decline in the last 12 months for which data are available, says the tobacco committee of the National Association of Attorneys General (www.naag.org).

The 378 billion cigarettes sold in 2005 was the lowest number since 1951, although the population has doubled over the same time period, says the association, citing figures compiled by the Tobacco Tax Bureau.

The association …
Autologous or Allogeneic Bone Marrow Transplantation Compared with Intensive Chemotherapy in Acute Myelogenous Leukemia
Authors: Robert A. Zittoun, Franco Mandelli, Roel Willemze, Theo de Witte, Boris Labar, Luigi Resegotti, Franco Leoni, Eugenio Damasio, Giuseppe Visani, Giuseppe Papa, Francesco Caronia, Marcel Hayat, Pierre Stryckmans, Bruno Rotoli, Pietro Leoni, Marc E. Peetermans, Murielle Dardenne, Maria Luce Vegna, Maria Concetta Petti, Gabriel Solbu, Stefan Suciu
Journal: New England Journal of Medicine (1995)

Allogeneic or autologous bone marrow transplantation and intensive consolidation chemotherapy are used to treat acute myelogenous leukemia in a first complete remission.
Synthesis and processing of molecules bearing thymus leukemia antigen.
Authors: E Rothenberg, E A Boyse
Journal: The Journal of Experimental Medicine (1979)

Thymus-leukemia (TL) antigens are expressed in murine lymphocytes under strict developmental regulation. To elucidate the molecular basis of TL expression, we have identified the molecular species that react with TL antiserum. At least three species can be resolved by metabolic radiolabeling of thymocytes and ASL1 leukemia cells, lysis, immune precipitation, and sodium dodecyl sulfate-polyacrylamide. After a brief incubation with [35S]methionine, the only radioactive molecule recognized by TL antiserum is a homogeneous species with an apparent Mr of 45,000 daltons. This molecule, 45K TL, includes high-mannose-type carbohydrate attached to a 45,000 dalton glycosidase-resistant backbone. In this form, 45K, it is never exposed on the cell surface. If pulse-labeled cells are further incubated with nonradioactive methionine before lysis, however, radioactivity disappears from the 45K TL species and appears in the slower migrating species 46K and 48K TL. Thus, 46K and 48K appear to represent products generated from the 45K TL precursor by posttranslational modification. These TL forms are displayed on the cell surface; they lack high-mannose carbohydrate but evidently include acidic complex-type carbohydrate. Normal thymocytes from Qa:Tla-negative mice lack not only the surface forms of TL but also the intracellular 45K TL form. Peripheral lymphoid cells of Qa:Tla-positive mice synthesize none of these TL species. But the TL antiserum, which contains Qa antibody, recognizes a distinct gene product in spleen and thymus of Qa-Tla-positive mice. In its pulse-labeled form, this molecule, which may represent Qa-1, has an apparent Mr of 44,000 daltons, and consists of a glycosidase-resistant polypeptide core of only 35,000 daltons linked to more high mannose carbohydrate than 45K TL.