tbuckley/cabot-search huggingface dataset:
Vascular Proliferation Is Important for Clinical Progress of Endometrial Cancer
Authors: Ingunn M. Stefansson, Helga B. Salvesen, Lars A. Akslen
Journal: Cancer Research (2006)

Abstract Angiogenesis is essential for tumor growth, invasion, and metastatic spread. Whereas microvessel density (MVD) has been widely used as a measure of tumor-associated angiogenesis, we now wanted to examine the significance of other angiogenic markers, especially vascular proliferation (by Ki-67/factor VIII staining) and the degree of pericyte coverage [by α-smooth muscle actin (α-SMA)/factor VIII staining], in a large and population-based series of endometrial carcinoma with complete follow-up. Due to limited information on the role of lymphangiogenesis in these tumors, lymphatic vessel density (LVD) by LYVE-1 staining was also determined, as well as selected angiogenic factors [vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D and basic fibroblast growth factor (bFGF)], which could possibly be related to vascular proliferation and lymphangiogenesis. The information on angiogenic phenotype was related to clinicopathologic features and disease progress. Median vascular proliferation, as estimated by vascular proliferation index (VPI), was 3.9% and high VPI was associated with features of aggressive tumors and decreased survival. The prognostic effect of VPI was superior to that of MVD. Presence of pericyte coverage, as estimated by the α-SMA index (SMAI), was 35% and low SMAI was significantly associated with vascular invasion by tumor cells and impaired prognosis. Peritumoral lymphatic vessels (LVD-pt) were found in 39.5% of the cases and high LVD-pt was significantly associated with aggressive tumor features and decreased survival. In multivariate survival analysis, only the extent of vascular proliferation had independent prognostic effect, in addition to well-known clinicopathologic factors, whereas MVD did not have significant prognostic value. In conclusion, our study indicates that vascular proliferation is a meaningful variable in assessing the angiogenic phenotype of endometrial carcinoma. (Cancer Res 2006; 66(6): 3303-9)
Biological neuroscience is only as radical as the evolution of mind
Authors: Terry Blumenthal, James Schirillo
Journal: Behavioral and Brain Sciences (1999)

A biological neuroscientific theory must acknowledge that the function of a neurological system is to produce behaviors that promote survival. Thus, unlike what Gold &amp; Stoljar claim, function and behavior are the province of neurobiology and cannot be relegated to the field of psychological phenomena, which would then trivialize the radical doctrine if accepted. One possible advantage of adopting such a (correctly revised) radical doctrine is that it might ultimately produce a successful, evolutionarily based, theory of mind.
The dynamics of prognostic indicators: toward earlier identification of dialysis patients with a high risk of dying
Authors: Charles Chazot, Guillaume Jean
Journal: Kidney International (2013)

Mortality remains stubbornly high in patients receiving chronic dialysis treatment. Identifying at-risk patients is essential for implementation of supportive therapies. The Monitoring Dialysis Outcomes (MONDO) database shows that in 40,000 dialysis patients worldwide who died, systolic blood pressure, interdialytic weight gain, and serum albumin declined progressively, and C-reactive protein increased more than 12 months before death, indicating that predictive models may be developed to enable nephrologists to improve the clinical outcome of dialysis patients.
Chlamydia pneumoniae: defining the clinical spectrum of infection requires precise laboratory diagnosis.
Authors: S J Bourke, N F Lightfoot
Journal: Thorax (1995)

To assess the utility of PCR-enzyme immunoassay (EIA) for diagnosis of acute infection with C pneumoniae, we compared tissue culture, PCR-EIA, direct fluorescent-antibody (DFA) stain, and serology in studies with 56 patients with respiratory symptoms and 80 asymptomatic persons.Thirty five patients were positive by either culture or PCR-EIA, and 101 were negative by both assays.Thirty specimens from symptomatic patients and one from an asymptomatic patient were culture positive; 23 of these were also PCR-EIA positive.Of the eight culture-positive, PCR-EIA-negative specimens, five were DFA negative and three were DFA positive.Four additional specimens were culture negative and PCR-EIA positive; of these, three were DFA positive and one was DFA negative.When we used culture- and/or DFA-positive results as a reference or "gold standard", the sensitivity and specificity of PCR were 76-5 and 99.0% respectively.When we used PCR-and/or DFA-positive results as the reference, the sensitivity of culture was 87*5%.On the basis of single acute serum specimens, only 8 of these 35 patients had diagnostic antibody titres.Of the asymptomatic patients, 75% had immunoglobulin G or immunoglobulin M antibody to C pneumoniae; 15 (18.8%) of these had antibody levels considered to be diagnostic of acute infection.This multicentre study indicates that culture and/or PCR-EIA is more reliable for prompt diagnosis of C pneumoniae infection than single-point serology alone.
The University and Primary Medical Care
Authors: Robert J. Haggerty
Journal: New England Journal of Medicine (1969)

Abstract Primary medical-care programs are legitimate and central concerns of every university medical school. Sufficient engagement in the community to learn how better to meet the needs of large numbers of patients who are now without care is necessary, but overcommitment to service programs should be avoided. The role of the university is to develop new programs, study them and especially teach within them. Health-services research offers an intellectually rewarding and academically legitimate field for faculty members engaged in this area. They should use the knowledge developed in such research to help forge public policy for health, but only to the degree that they have data. When they move beyond the data they cease to be experts. Some must seek to combine the difficult tasks of remaining experienced clinicians, doing research, advising on public policy and teaching. Of these, teaching is the unique function of the university and must be a part of any university primary-care program.
Chronic Unilateral Eruption of Painful, Erythematous Papules and Nodules
Authors: Marigdalia K. Ramirez-Fort, Hung Q. Doan, Harrison P. Nguyen, Farhan Khan, Julia Kauffman, Lauren S. Campbell
Journal: JAMA Dermatology (2013)

A72-year-oldwhitewoman of German heritage presentedwith a 30-yearhistoryof several painful lesionson the left sideofherbody. Clinical examination revealednumerous tender, erythematouspapules and nodules over her left chest, flank, and lower extremity (Figure 1). The patient’s medical history was significant for hyperlipidemia, multiple uterine leiomyomas status after hysterectomy in 1972, and severe coronary artery disease status after coronary artery bypass grafting in 2004. The patient emigrated from GermanyshortlyafterWorldWar II; familialmedicalhistorywasnotavailable. Her medications were aspirin, warfarin, duloxetine, pregabalin, and atorvastatin. A shave biopsy was performed from a characteristic papule on the left lower extremity. Routine hematoxylin-eosin–stained sections are shown in Figure 2 and Figure 3. What is your diagnosis?
Co-artemether has been used in ambulatory treatment of falciparum malaria
Authors: S. Toovey
Journal: BMJ (2002)

EDITOR—D'Acremont et al report a study of the treatment of imported malaria in an ambulatory setting.1 We are the sole providers of care to a large group of non-immune expatriates and semi-immune Mozambicans in Maputo, diagnosing malaria by rapid antigen testing and microscopy. We report here on the treatment of non-immune patients with falciparum malaria.

Given the lack of adequate high level care facilities in Maputo, we have had to devise a treatment …
Decreased levels of coenzyme Q<sub>10</sub> in patients with bronchial asthma
Authors: F. Gazdík, A. Gvozdjáková, R. Nádvorníková, L. Repická, E. Jahnová, J. Kucharská, M. R. Piják, K. Gazdíková
Journal: Allergy (2002)

The contribution of free oxygen radicals in the pathogenesis of bronchial asthma is generally accepted. The modulation of antioxidative defence by supplementation with antioxidants represents additive therapy in complex management of disease. The aim of the study was to assess the levels of coenzyme Q10, alpha-tocopherol, and beta-carotene both in plasma and whole blood, and malondialdehyde (MDA) and eosinophil cationic protein (ECP) in plasma of asthmatics (As).Fifty-six As (15 males and 41 females) aged from 19 to 72 years (mean age 46 years) suffering from allergic asthma were enrolled into the study. The control group comprised 25 healthy volunteers (16 males, 9 females) aged 25-50 years.The concentrations of CoQ10 decreased significantly both in plasma and whole blood, compared with healthy volunteers (0.34 +/- 0.15 micromol/l vs. 0.52 +/- 0.15 micromol/l, 0.33 +/- 0.14 micromol/l vs. 0.50 +/- 0.13 micromol/l, P < 0.001, P< 0.001, respectively). The levels of alpha-tocopherol were decreased both in plasma and whole blood in comparison with controls [24.10 micromol/l (19.8; 30.5), vs. 33.20 micromol/l (28.25; 38.05), 17.22 +/- 6.45 micromol/l vs. 21.58 +/- 7.92 micromol/l, P= 0.006, P = 0.01, respectively]. The levels of MDA were elevated over the reference range in both groups (reference range < 4.5 micromol/l). No changes were seen in beta-carotene concentrations. Positive correlation was found between whole blood CoQ10 and alpha-tocopherol concentrations.Results of the study suggest a possible contribution of suboptimal concentrations of CoQ10 on antioxidative dysbalance in As and provide a rationale for its supplementation.
"Recto-cerebral Reflex" A Questionable Entity
Authors: Harold A. Wilkinson
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Is there really a "recto-cerebral reflex," as many of us have been taught? Is it really dangerous to distend manually the rectal sphincter of a patient with raised intracranial pressure for fear of causing an even further rise? No one will ever know how many rectal carcinomas have gone undetected (oft times when their detection would have helped to clarify the possibly metastatic cause of the raised intracranial pressure) or how much human suffering has been prolonged by the possibly unnecessary withholding of manual fecal disimpaction. Certainly the dangers of administering enemas to patients with raised intracranial pressure are well documented and are well known to physicians and nurses alike.<sup>1,2</sup>Distending the colon with fluid compresses abdominal veins and raises their intraluminal pressure. This pressure is in turn transmitted via paravertebral veins to the intrathecal space, causing a sharp rise in intracranial pressure. Manually compressing the
THE TREND OF PREVENTIVE MEDICINE IN THE UNITED STATES
Authors: JOHN A. FERRELL
Journal: JAMA (1923)

<h3>THE SCIENTIFIC BASIS OF PREVENTIVE MEDICINE</h3> Scientific discoveries of the last half century regarding disease have furnished a sound basis for the field of preventive medicine. Public and private agencies have been established to apply this knowledge. The record of reduction of deaths from controllable diseases is proof of their effectiveness. Additional knowledge of other diseases is needed, and there is a growing tendency to encourage research. <h3>ORGANIZATIONS FOR APPLYING PREVENTIVE MEDICINE</h3> The growth of organizations for applying preventive medicine has followed the development of knowledge of disease. The United States Public Health Service now has authority to engage in all activities that are proper functions of a national health department. It is a bureau of the Treasury Department. The collection of vital statistics and other public health activities are functions of other departments. The trend is toward consolidation of all federal health work into a single department. City health
Antibiotic prescribing and antibiotic resistance in community practice: retrospective study, 1996-8
Authors: J T Magee, E. L Pritchard, K. A Fitzgerald, F D J Dunstan, A J Howard
Journal: BMJ (1999)

Data on the susceptibility to antibiotics of coliform organisms in routine urine samples taken by general practitioners for diagnosis of urinary tract infections were collected from the Bangor, Cardiff, and Rhyl Public Health Laboratories and the East Glamorgan, Prince Charles, and Wrexham Maelor Hospitals. Data on the prescribing practices of surgeries were obtained from the Welsh Prescription Pricing Service Rates of prescribing (the number of prescriptions/1000 patients per year) and resistance rates (which excluded multiple isolates of organisms with the same susceptibility from the same patient) were calculated for each surgery. The use of broad spectrum penicillin formulations without a β lactamase inhibitor (such as ampicillin and amoxicillin) was estimated by subtracting the number of prescriptions for co-amoxiclav from the total number of prescriptions for all other broad spectrum penicillins. We use the term amoxicillin below to refer to these broad spectrum penicillins without a β lactamase inhibitor.

Resistance rates for surgeries which were based on fewer than 50 isolates were excluded, leaving data on about 30 000 isolates from 190 general practitioner surgeries serving about 1 200 000 patients. We sought to identify the effects of bias caused by the selective submission of urine samples by examining the relation between resistance rates and sampling (number of urine specimens/1000 registered patients) and the relation between positivity (number of coliform isolates/100 samples or 1000 registered patients) and prescribing or sampling.

The use of antibiotics and rates of resistance to antibiotics varied between surgeries; the correlation between the prescribing of an antibiotic and resistance to the same antibiotic was often significant (table) The correlation was also significant between the use of amoxicillin and resistance to trimethoprim and vice versa. Combined resistance to ampicillin and trimethoprim occurred in 21% (6782/32 532) of isolates and was significantly associated with the use of both trimethoprim and amoxicillin (P<0.001). The correlation between the use of amoxicillin and resistance to trimethoprim and vice versa was lost when strains exhibiting combined resistance to both agents were removed from the analysis.
Pharmacology Researchers Receive 1988 Nobel Prize
Authors: Charles Marwick
Journal: JAMA (1988)

DRUG RESEARCH clearly has the attention of the Nobel Prize committee. This year's Nobel Prize for Physiology or Medicine goes to three pioneering pharmacology researchers: George Hitchings, MD, and Gertrude Elion, DSc, Burroughs Wellcome Co, Research Triangle Park, NC, and Sir James Black, King's College Hospital Medical School, London. The committee noted: "While drug development had earlier mainly been built on chemical modification of natural products, they introduced a more rational approach based on the understanding of basic biochemical and physiological processes." From the prizewinners' work have come a whole string of drugs useful for treating leukemia, manipulating the immune response, controlling herpes infections, and managing gout, hypertension, heart disease, and gastric ulcers. Hitchings, a biochemist, arrived at Burroughs Wellcome in 1942 when the company was in Tuckahoe, NY. "When I started," he recalls, "it was to study antimetabolites of nucleic acid biosynthesis using analogues of the bases purine and
Dutch academics criticise suicide claims made in American psychiatry journal
Authors: Tony Sheldon
Journal: BMJ (2008)

Claims in an influential scientific journal of a link between a leap in suicides among young people in the Netherlands and a fall in prescriptions for selective serotonin reuptake inhibitors (SSRIs) has been condemned in the Netherlands as “astonishing” and “misleading.”

Researchers led by Robert Gibbons, of Illinois University in Chicago, have reported that, following warnings from regulatory authorities, SSRI prescriptions for Dutch youths decreased between 2003 and 2005 by approximately 22% ( American Journal of Psychiatry 2007;164:1356-63; reported in BMJ  2007;335:531).

During the same period, Dutch youth suicide rates increased …
Immunomodulation by thalidomide and thalidomide analogues
Authors: Laura G Corral, Gilla Kaplan
Journal: Annals of the Rheumatic Diseases (1999)

Tumour necrosis factor α (TNFα), a key cytokine involved in the host immune response, also contributes to the pathogenesis of both infectious and autoimmune diseases. To ameliorate the pathology resulting from TNFα in these clinical settings, strategies for the inhibition of this cytokine have been developed. Our previous work has shown that the drug thalidomide is a partial inhibitor of TNFα production in vivo. For example, when leprosy patients suffering from erythema nodosum leprosum (ENL) are treated with thalidomide, the increased serum TNFα concentrations characteristic of this syndrome are reduced, with a concomitant improvement in clinical symptoms. Similarly, we have found that in patients with tuberculosis, with or without HIV infection, short-term thalidomide treatment reduces plasma TNFα levels in association with an accelerated weight gain. In vitro, we have also shown that thalidomide partially inhibits TNFα produced by human peripheral blood mononuclear cells (PBMC) responding to stimulation with lipopolysaccharide (LPS). Recently, we found that thalidomide can also act as a costimulatory signal for T cell activation in vitro resulting in increased production of interleukin 2 (IL2) and interferon γ (IFNγ). We also observed a bi-directional effect on IL12 production: IL12 production is inhibited by thalidomide when PBMC are stimulated with LPS, however, IL12 production is increased in the presence of the drug when cells are stimulated via the T cell receptor. The latter effect is associated with upregulation of T cell CD40 ligand (CD40L) expression. Thus, in addition to its monocyte inhibitory activity, thalidomide exerts a costimulatory or adjuvant effect on T cell responses. This combination of effects may contribute to the immunomodulating properties of the drug.

To obtain drugs with increased anti-TNFα activity that have reduced or absent toxicities, novel TNFα inhibitors were designed using thalidomide as template. These thalidomide analogues were found to be up to 50 000 times …
No Lighting Up in More Workplaces, Other Sites
Authors: Phil Gunby
Journal: JAMA (1994)

THE NEXT few days should bring a lot of bad news for tobacco companies.  M. Joycelyn Elders, MD, surgeon general of the US Public Health Service, indicates that she is about to release a report on problems associated with smoking by young people.  Also expected soon, probably no later than the end of March, are smoking regulations from the US Department of Labor. To be issued by the department's Occupational Safety and Health Administration (OSHA), these regulations are intended to protect nonsmokers from second-hand smoke in the workplace.  Nonfarm workplaces with more than one employee are subject to OSHA regulations, which govern more than 90 million workers at more than 6 million work sites.  While these developments are pending, Arby's Inc has announced that it will ban smoking in its 257 corporate-owned restaurants by summer and urge its nearly 2000 franchise holders to go smoke free in their outlets also.
Energy intake and weight gain of very low birthweight babies fed raw expressed breast milk.
Authors: D P Davies, D Kennedy
Journal: BMJ (1982)

altogether surprising for as Paton put it: "If an antagonist can attach to a receptor, why does it not excite ?'16Ashford et al7 indeed replied affirmatively when they showed that small doses of atropine potentiated the effects of acetylcholine on smooth muscle (guinea- pig ileum).An analogous process might occur in the airways of some atopic asthmatics.Whatever the explanation it has now been shown that the paradoxical response of the forced expiratory volume in one second to inhaled anticholinergic drugs (including iprat- ropium brornide) can be abolished by adequate control of asthma with corticosteroid drugs.5
A NEEDLE EXTRACTOR.
Authors: P. C. CLEMENSEN
Journal: JAMA (1902)

The difficulty of extracting a needle after it has been inserted into dense tissues, especially if threaded with heavy suture material, is one with which every surgeon is familiar. Inasmuch as it is often impossible to let go with the needle holder before getting a hold of the point of the needle with something, one mostly resorts to extract the needle with a pair of hemostatic forceps, or if it is a fine needle a pair of ordinary tissue forceps is used. Neither of these instruments are well adapted for the purpose; the hemostatics are unhandy, and often crush the needle, while the tissue forceps slip and nearly always spoil the point of the needle. In offering the present needle extractor I have added no distinctly new instrument to the already great number, but have merely tried to modify a pair of heavy tissue forceps to the special use of
Abstract 5717: The Poly (ADP-Ribose) Polymerase-1 Inhibitor, AZD2281, enhances radiation response of breast cancer cells by inhibiting DNA repair
Authors: Meghna Mehta, Anupama Munshi
Journal: Cancer Research (2012)

Abstract PARP-1 is a nuclear enzyme essential for base excision repair (BER), SSB, and possibly other DNA repair processes and an important damage sensor. It has been identified as a synthetic lethal target in BRCA1/2 breast cancers. PARP-1 is activated after binding DNA strand breaks and uses NAD+ as a substrate to form long branched polymers of poly(ADP-ribose) (PAR). PARP-1 mediated poly(ADP-ribosylation) recruits various nuclear acceptor proteins, such as XRCC1, histones, and PARP-1 itself, to assemble other repair complexes to execute DNA repair. As a result, PARP inhibitors are being developed for cancer therapy due to their ability to sensitize cells to DNA-damaging agents. Thus, in this current study, we hypothesized that enhanced radiosensitivity of breast cancer may be achieved by combining ionizing radiation (IR) with the PARP inhibitor, AZD2281. We studied the effects of combined treatment of radiation and AZD2281 on three human breast cancer cell lines, MCF-7, MDA-MB-231 and Hs578t. Cells were treated either with vehicle alone or with AZD2281 (4μM for 24hrs for MCF-7; 2μM for 24hrs for the MDA-MB-231 and Hs578t cells). Clonogenic cell survival assay showed that AZD2281 enhanced tumor cell radiosensitivity with the survival factor at 2Gy (SF2) being reduced from 26%, 52.8%, and 51.5% in vehicle treated to 18.5%, 27.8%, and 45.52% in AZD2281-treated MCF-7, MDA-MB-231 and Hs578t cells respectively. As an initial investigation into the mechanism responsible for AZD2281-mediated radiosensitization, we examined the effect of AZD2281 treatment on the expression of proteins known to be involved in the repair of radiation-induced DSBs. Western blot analysis for Ku70, Ku86, and DNA-PKcs demonstrated a decrease in the levels of all three proteins following AZD2281 treatment in the breast cancer cell lines tested. As an additional test of our hypothesis that AZD2281 impairs the repair of damaged DNA, γ-H2AX foci were assessed as indicators of DNA damage. PARP inhibition markedly enhanced γ-H2AX persistence in the MCF-7 and MDA-MB-231 cell lines suggestive of the presence of persistent DSBs. These data support the use of the PARP inhibitor, AZD2281, in combination with radiation therapy as an innovative treatment strategy to potentially improve outcomes in breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5717. doi:1538-7445.AM2012-5717