tbuckley/cabot-search huggingface dataset:
Coronary Atherosclerosis, Coronary Collaterals, and Their Relation to Cardiac Function
Authors: Richard H. Helfant, Harvey G. Kemp, Richard Gorlin
Journal: Annals of Internal Medicine (1970)

In subjects with coronary artery disease demonstrated by selective coronary arteriography there was a progressively higher prevalence of both ventriculographic abnormalities (asynergy) and collaterals in one-, two-, and three-vessel disease groups, respectively, although no association was demonstrable between these two abnormalities. Subjects with ventriculographic abnormalities had more hemodynamic dysfunction when compared with those with normal ventricular contraction, but there was no correlation between number of coronary vessels involved and hemodynamic abnormalities. The findings suggest that although an abnormal ventricular contraction pattern is associated with hemodynamic dysfunction, the presence of collaterals does not protect from the development of asynergy or hemodynamic abnormalities.
A Role for Stroma-Derived Annexin A1 as Mediator in the Control of Genetic Susceptibility to T-Cell Lymphoblastic Malignancies through Prostaglandin E2 Secretion
Authors: Javier Santos, Laura González-Sánchez, María Matabuena-deYzaguirre, María Villa-Morales, Patricia Cozar, Pilar López-Nieva, Pablo Fernández-Navarro, Manuel Fresno, Manuel D. Díaz-Muñoz, Jean-Louis Guenet, Xavier Montagutelli, José Fernández-Piqueras
Journal: Cancer Research (2009)

Cancer susceptibility is essentially attributable to multiple low-penetrance genes. Using interspecific consomic and congenic mice between the tumor-resistant SEG/Pas and the tumor-sensitive C57BL/6J strains, a region on chromosome 19 involved in the genetic resistance to gamma-irradiation-induced T-cell lymphomas (Tlyr1) has been identified. Through the development of nonoverlapping subcongenic strains, it has been further shown that Anxa1 may be a candidate resistance gene on the basis of its differential expression in thymus stroma cells after gamma-radiation exposure. In addition, thymus stroma cells of thymic lymphomas exhibited a significant reduction in the expression levels of Anxa1. Interestingly, the activity of Anxa1 relies on prostaglandin E(2) (PGE(2)) induction that brings about apoptosis in thymocytes. In fact, in vitro transfection experiments revealed that PGE(2) production was enhanced when HEK 293 cells were transfected with full-length cDNAs of Anxa1, with PGE(2) production in the cells transfected with the allele of the resistant strain (Anxa1(Tyr)) being higher than that in cells transfected with the allele of the susceptible strain (Anxa1(Phe)). Furthermore, the presence of this compound in the medium induced apoptosis of immature CD4(+)CD8(+)CD3(low) cells in a dose-dependent manner. These results improve our knowledge of the molecular mechanisms triggering T-cell lymphoblastic lymphoma development while highlighting the relevance of the stroma in controlling genetic susceptibility and the use of PGE(2) as a new therapeutic approach in T-cell hematologic malignancies.
Role of CD4 molecule in the induction of interleukin 2 and interleukin 2 receptor in class II major histocompatibility complex-restricted antigen-specific T helper clones. T cell receptor/CD3 complex transmits CD4-dependent and CD4-independent signals.
Authors: N Oyaizu, N Chirmule, S Pahwa
Journal: Journal of Clinical Investigation (1992)

The CD4 molecule plays an essential role in antigen-induced activation of T helper (Th) cells, but its contribution to signal transduction events resulting in physiologic T cell function is ill defined. By utilizing anti-CD4 monoclonal antibodies (MAbs) that recognize distinct epitopes of CD4, we have investigated the role of CD4 molecule in antigen-induced interleukin 2 (IL-2) and IL-2 receptor (IL-2R) alpha chain expression in class II major histocompatibility complex-restricted antigen-specific human Th clones. Pretreatment of the Th clones with Leu3a resulted in a dose-dependent suppression of antigen-induced proliferative responses, inositol phosphate accumulation, increase in free cytoplasmic calcium ions ([Ca2+]i), IL-2 mRNA accumulation, IL-2 secretion, and membrane IL-2R expression. IL-2R mRNA accumulation, however, was unaffected even at highest Leu3a concentrations. Leu3a treatment did not affect bypass activation of T cells with PMA plus ionomycin or activation via CD2 molecule. The MAb OKT4, which binds another domain of CD4, was not inhibitory. These results suggest that after T cell antigen receptor-CD3 activation, IL-2 gene induction, IL-2 secretion, and membrane IL-2R expression are absolutely dependent upon participation of CD4 molecules, phosphatidylinositol (PI) hydrolysis, and increase in [Ca2+]i. The requirement for IL-2R gene induction, however, occurs independently of CD4 molecule participation and PI hydrolysis.
Cancer of the Gastrointestinal Tract
Authors: Philip Rubin
Journal: JAMA (1974)

FOR UNEXPLAINED reasons, the occurrence of stomach cancer has declined in the United States during the past few decades; its mortality remains high, however, and the dread associated with this disease has not diminished. Deaths attributed to gastric cancer are exceeded only by those from neoplasms of the lung, colonrectum, and breast.<sup>1</sup>An estimated 20,000 patients will develop stomach cancer in the United States this year; eventually 85% will die.<sup>1</sup> Stomach cancer has not diminished in incidence around the world, however; the highest frequency occurs in Japan, Iceland, Finland, and Chile.<sup>2</sup>More than 60% of all stomach cancers occur in persons 65 years of age and older. It is predominant in men, and is most common among lower socioeconomic groups. The prevalence among farmers and laborers is twice that of craftsmen and white-collar workers. When occupation was related to diet, farmers consumed more smoked and singed foods
A guide to temporary pacing.
Authors: A. Fitzpatrick, R. Sutton
Journal: BMJ (1992)

Temporary cardiac pacing is a necessary skill for any doctor concerned with managing patients with life threatening bradycardia.Often, in the district hospital setting, an inexperienced member of an acute medical team will be called on to support the heart rate of a sick patient by inserting a temporary pacing electrode.Apart from knowing when to institute pacing, this requires proficient central venous cannulation and manual dexterity for stable positioning of the catheter.Temporary pacing is probably more difficult than permanent pacing for which the electrodes have a pliant stylet, and can be steered to some extent.Also, temporary pacing commonly is required under the most stressful conditions when the patient's life may depend on rapidly achieving and maintaining reliable pacing.Because temporary pacing may be difficult and may be undertaken by junior staff, factors facilitating the procedure must be optimised.All junior staff should have a clear idea of the indications for pacing, both temporary and permanent.The location of, and access to, pacing facilities should be known to all staff who may be concerned with temporary pacing.Once inside the pacing room it is the doctor's responsibility to know exactly what equipment is available and to direct nursing and radiographic staff.
The role of bacterial biofilm in persistent infections and control strategies
Authors: Li Chen, Yu‐mei Wen
Journal: International Journal of Oral Science (2011)

Bacterial biofilms can be viewed as a specific type of persistent bacterial infection. After initial invasion, microbes can attach to living and non-living surfaces, such as prosthetics and indwelling medical devices, and form a biofilm composed of extracellular polysaccharides, proteins, and other components. In hosts, biofilm formation may trigger drug resistance and inflammation, resulting in persistent infections. The clinical aspects of biofilm formation and leading strategies for biofilm inhibitors will be discussed in this mini-review.
Abstract 741: Sunitinib plus hormone ablation and radiation therapy for patients with high-risk localized prostate cancer: Results from a multi-institutional phase I study
Authors: Paul G. Corn, Danny Song, Elisabeth Heath, Jordan Maier, Raymond Meyn, Deborah Kuban, Thomas DiPetrillo, Paul Mathew
Journal: Cancer Research (2012)

Abstract Background: Novel strategies are needed to improve the long-term outcomes of patients (pts) with high-risk prostate cancer treated with hormonal ablation and external beam radiation therapy (XRT). Preclinical data suggest that angiogenesis inhibitors normalize vasculature, reduce hypoxia, and improve the therapeutic index of XRT. To assess the feasibility of combined VEGFR/PDGFR inhibition in combination with XRT, a Phase I study with sunitinib was initiated. Methods: Seventeen men with adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or PSA &amp;gt; 20ng/ml received initial hormonal ablation (leuprolide 22.5mg every 12 weeks + oral bicalutamide 50mg daily) for 4-8 weeks prior to oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks post XRT (prostate and proximal seminal vesicles received 75.6 Gy in 42 fractions with at least 50 Gy for the distal seminal vesicles). A 3+3 sequential dose-escalation design was employed to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose (MTD) of sunitinib. Results: The first 4 pts enrolled on 37.5 mg experienced a DLT during lead-in. *With 2 pts unexpectedly experiencing Grade 3 neutropenia and a third experiencing Grade 3 thrombocytopenia, a drug-interaction with bicalutamide was suspected. The protocol was revised to replace these pts and omit concurrent bicalutamide. Of these first 4 pts, 3 were dose reduced to 25 mg and successfully completed full treatment, while 1 pt withdrew. Of the next 3 pts subsequently enrolled at 37.5 mg, 2 of 3 on concurrent therapy have experienced DLTs (G3 diarrhea with concomitant sunitinib-induced thyrotoxicosis; G3 proctitis). Conclusions: Using a daily dosing regimen and a lead-in phase, the MTD of concurrent sunitinib, hormonal ablation and XRT was 37.5mg daily. The recommended Phase 2 dose of sunitinib for further study is 25mg daily. 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 741. doi:1538-7445.AM2012-741
OCULAR DISEASE OCCURRING IN THE COURSE OF NONDYSENTERIC AMEBIASIS
Authors: LLOYD MILLS
Journal: JAMA (1926)

In November, 1923, I<sup>1</sup>reported the first recorded association of iritis and nondysenteric amebiasis. Three cases were described in detail and a comprehensive survey was made of the known and possible rôles of protozoa and flagellates in the production of general and of ocular disease. The present study supplements the original observations, to which the reader is referred for much necessary background. It was self-evident, after the connection between chronic iritis and nondysenteric amebiasis had been demonstrated convincingly, that an intestinal disorder of sufficient pathogenicity to lead to the production of characteristic iridocyclitis, with cataract, glaucoma and blindness or enucleation as not rare sequels, with justice might be considered as a possible source of other chronic, resistant and obscure ocular inflammations. The causes of many cases of choroiditis, glaucoma, retinitis, retinal detachment, cataract, episcleritis and chronic conjunctivitis are never found, in spite of the ordinary search. The present situation
Elizabeth Joan Stokes
Authors: G. Ridgway, B. Harrison
Journal: BMJ (2010)

Dr Elizabeth Joan Stokes (“Joan”) died on 28 January 2010 aged 97. Dr Stokes steered the specialty of clinical microbiology from its emergence from mainstream pathology in the 1960s to a discipline in its own right. Joan graduated from University College Hospital Medical School in 1937, obtaining MB BS and LRCP MRCS. Following house appointments and a casualty medical officer post at UCH she was briefly in general practice. After obtaining MRCP in 1939, Joan returned to UCH in 1940 as registrar to Sir Thomas Lewis and to the medical unit. UCH was evacuated to Cardiff in …
Should women with HIV, or at high risk of contracting HIV, use progestogen-containing contraception?
Authors: S. L. Giles, F. Lester
Journal: BMJ (2013)

Nearly 150 million women worldwide use hormonal methods of contraception, predominantly oral contraceptives taken daily (both combined hormonal pills and progestogen-only pills for the purpose of this article) and long acting injectables such as depot medroxyprogesterone acetate and norethisterone enantate.1 When used correctly, these are highly effective in preventing pregnancy and are reversible. Side effects of medroxyprogesterone are similar in those who are seropositive for HIV and those who are HIV negative,2 and antiretroviral therapy does not reduce its effectiveness.3 However, antiretroviral therapy can make oral contraceptives less effective at preventing pregnancy, and oral contraceptives can increase antiretroviral drugs’ toxicity.3

Concerns have been raised about possible harmful effects of hormonal contraception in patients infected with HIV and those at high risk of contracting HIV. These effects can be considered in three main categories: HIV acquisition, HIV infectivity, and rate of progression of HIV. Several biologically plausible mechanisms have been proposed for these effects, including effects on genital HIV viral shedding, vaginal epithelial thickness, degree of cervical ectopy, or local and systemic immune responses.4 However, there is little consistent evidence.

Any potential for harm is important given that in sub-Saharan Africa, women of childbearing age are disproportionately affected by HIV. It is essential to offer women the opportunity to prevent HIV acquisition, not only for their own health but to prevent mother to child transmission. The most upstream means of primary prevention for HIV is preventing unintended pregnancy in the first place. Disease progression puts the woman at risk of opportunistic infections and increases the risk of transmitting the disease to an uninfected partner.

However, it is equally important to avoid denying access to contraceptives without adequate evidence, since those areas where unintended pregnancy poses the greatest threat to women’s lives are often the same areas …
Abstract 1654: Compensatory insulin receptor (IR) activation upon inhibition of insulin-like growth factor receptor (IGF-1R): Rationale for co-targeting IGF-1R and IR in cancer
Authors: Elizabeth Buck, Prafulla Gokhale, Susan Koujak, Alexandra Eyzaguirre, Robert Wild, David Epstein, Jonathan Pachter, Mark Miglarese
Journal: Cancer Research (2010)

Abstract The insulin-like growth factor receptor (IGF-1R) is a receptor tyrosine kinase (RTK) and a critical mediator of signaling through the PI3K-AKT pathway. IGF-1R is required for oncogenic transformation and tumorigenesis, and inhibiton of IGF-1R results in reduced proliferation and survival of tumor cells. These observations have spurred intense drug discovery and development efforts for both biologic and small molecule IGF-1R inhibitors for the treatment of cancer. The ability for one RTK to compensate for another to maintain growth and survival signaling in tumor cells is emerging as a common mechanism of resistance to anti-tumor agents that selectively target individual RTKs. As IGF-1R is structurally and functionally related to the insulin receptor (IR), and IR can also activate tumor cell AKT signaling and cellular transformation, we asked whether IR signaling can contribute to resistance to IGF-1R inhibition in tumor cells. In a panel of human tumor cell lines, IGF-1R/IR crosstalk was observed after treatment with a selective anti-IGF-1R monoclonal antibody, MAB391. Tumor cells treated with MAB391 responded with a compensatory increase in phospho-IR, which was also associated with an inability to fully inhibit phospho-IRS1 and phospho-AKT. In contrast, treatment with OSI-906, a small molecule dual kinase inhibitor of IGF-1R and IR, resulted in enhanced inhibition of the IRS1-AKT signaling pathway. OSI-906 showed superior efficacy compared to MAB391 in human tumor xenograft models where both phospho-IR and phospho-IGF-1R were detectable, and presumably both receptors were required by tumor cells for growth and/or survival. Both insulin and IGF-2 can activate the IR-AKT pathway and we show that treatment with either growth factor resulted in decreased sensitivity of tumor cells to MAB391, but not OSI-906. In tumor cells with an autocrine IGF-2 signaling loop, both OSI-906 and an anti-IGF-2 neutralizing antibody reduced phospho-IR and phospho-AKT levels, whereas MAB391 was ineffective. Collectively, these data indicate that OSI-906, which co-targets IGF-1R and IR, may provide superior efficacy as compared to agents that selectively target only IGF-1R. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1654.
Occupational asthma induced by aniseed
Authors: J. Fraj, A. Lezaun, C. Coláas, F. Duce, M. A. Domínguez, M. D. Alonso
Journal: Allergy (1996)

This report deals with clinical and immunologic studies in a butcher with work‐related asthma. Both the positive methacholine inhalation test and the significant changes observed in PEFR measurements supported the diagnosis of asthma. The significant fall observed in PEFR measurements when the patient handled aniseed supported the diagnosis of occupationa asthma. Skin prick tests carried out with 13 spices showed positive reactions only to aniseed extract. The patient had high levels of specific antianiseed IgE antibodies. The bronchial challenge test with an aniseed extract showed an immediate response without a late response. These findings suggest that the respiratory symptoms in our patient were induced by the inhalation of aniseed dust through an IgE‐mediated immunologic mechanism of immediate hypersensitivity. This study established the diagnosis of occupational asthma from aniseed dust sensitization.
Evidence of Gene Conversion Associated with a Selective Sweep in Drosophila melanogaster
Authors: Sascha Glinka, David De Lorenzo, Wolfgang Stephan
Journal: Molecular Biology and Evolution (2006)

Since Drosophila melanogaster colonized Europe from tropical Africa 10 to 15 thousand years ago, it is expected that adaptation has played a major role in this species in recent times. A previously conducted multilocus scan of noncoding DNA sequences on the X chromosome in an ancestral and a derived population of D. melanogaster revealed that some loci have been affected by directional selection in the European population. We investigated if the pattern of DNA sequence polymorphism in a region surrounding one of these loci can be explained by a hitchhiking event. We found strong evidence that the studied region around the gene unc-119 was shaped by a recent selective sweep, including a valley of reduced heterozygosity of 83.4 kb, a skew in the frequency spectrum, and significant linkage disequilibrium on one side of the valley. This region, however, was interrupted by gene conversion events leading to a strong haplotype structure in the center of the valley of reduced variation.
STATE SUPERVISION OF PRIVATE HOSPITALS AND NURSING HOMES
Authors: Ellen C. Potter
Journal: JAMA (1928)

To the Editor:  —Your readers may be interested in a recent development in New Jersey relating to  hospitals and  homes. Throughout the country such agencies are, for the most part, as you are aware, without inspection and supervision by public authorities and in many instances the credulous public pays large fees for inadequate service. In some instances, the type of work done in these institutions has been unethical. New Jersey has had a law providing for the inspection and licensing of  homes, but the act gave no adequate powers to the department of institutions and agencies controlling unethical or inadequately equipped and administered institutions of this sort, nor did the law appear to reach the private hospital unless the term nursing  was construed in the light of the  home in England.  At the recent session of the legislature the original act was amended to include
Vitamin A supplements and mortality related to measles: a randomised clinical trial.
Authors: A J Barclay, A Foster, A Sommer
Journal: BMJ (1987)

One hundred and eighty children admitted with measles were randomly allocated to receive routine treatment alone or with additional large doses of vitamin A (200,000 IU orally immediately and again the next day). Baseline characteristics of the two groups were virtually identical for age, severity of measles, and vitamin A and general nutritional states. In 91% of the children serum vitamin A concentrations were less than 0.56 mumol/l. Of the 88 subjects given vitamin A supplements, six (7%) died; of the 92 controls, 12 (13%) died (p = 0.13). This difference in mortality was most obvious for children aged under 2 years (one death out of 46 children receiving supplements versus seven deaths out of 42 controls; p less than 0.05) and for cases complicated by croup or laryngotracheobronchitis. Mortality was several times higher in marasmic than in better nourished children, regardless of study allocation (p less than 0.01).
Sclerostin Inhibition for Osteoporosis — A New Approach
Authors: Carolyn B. Becker
Journal: New England Journal of Medicine (2014)

Effective new therapies are still needed for people with osteoporosis. In 2002, the introduction of teriparatide, or recombinant parathyroid hormone (PTH [1-34]), opened a promising chapter in osteoporosis care.1 For the first time, there was an anabolic agent that significantly increased bone mineral density (BMD), reduced fracture risk, and restored bone architecture back to, or close to, normal. However, despite an impressive track record of both safety and efficacy, teriparatide has had a limited clinical reach as compared with other agents, largely owing to its requirement for daily subcutaneous injection, a black-box warning about osteosarcoma in rats, and its high . . .
Iatrogenic duodenal perforations caused by endoscopic biliary stenting and stent migration: an update
Authors: R. Saranga Bharathi, P. Rao, K. Ghosh
Journal: Endoscopy (2006)

Endoscopic biliary stenting is the preferred method of decompression in obstructive jaundice. Duodenal perforations caused during stenting and stent migration are rare but life-threatening complications, and require judicious management. With the increasing use of therapeutic endoscopy, an awareness of these complications is becoming important in our surgical practice. Advances in interventional radiology, endoscopy, and laparoscopy have enhanced the scope and reduced the morbidity of both conservative and surgical treatments of these perforations. This article presents an update on the current state of our knowledge on the science and the management of this complication.
The Rh Factor and Hepatomegaly and Splenomegaly in the Young
Authors: R. J. Drummond, A. G. Watkins
Journal: BMJ (1946)

MEDICAL JOURNAXL also states that the relative frequency of gene R" to gene R2 as compared with R' to R' indicates that his mythical, gene locus c lies between d and e.However, these statements are based entirely on the findings in England and disregard the findings in other countries.In America, for example, the relative fre- quency of R' to R" is reversed, while in negroes the frequency of r°(42.1%) is quite different from the sum of R' (2.7%) and R" (none found).'7As a result Fisher's theory leads to a contradiction.In my opinion a much more plausible explana- tion is that the genes ro, R', and R" arose by mutation.Thus the high frequency of gene -ro and of the intermediate R genes, as well as the intermediate gene A1, 2, suggests that the peculiar distribution among negroes is due to a higher mutation rate in this race.