tbuckley/cabot-search huggingface dataset:
Absence of anaplastic lymphoma kinase (ALK) and Epstein-Barr virus gene products in primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis
Authors: H. HERBST, C. SANDER, M. TRONNIEK, H. KUTZNER, H. HÜGEL, P. KAUDEWITZ
Journal: British Journal of Dermatology (1997)

The prevalence of the t(2;5)(p23;q35) and/or anaplastic lymphoma kinase (ALK) gene products in cutaneous anaplastic large cell (ALC) lymphomas and a potential precursor lesion, lymphomatoid papulosis (LyP), is controversial. ALK gene products, which are absent from normal lymphohaematopoietic cells, are a phenotypic marker of lymphomas carrying the t(2;5). We used in situ hybridization and immunohistology to screen 14 cutaneous ALC lymphomas, 21 cases of LyP, and one nodal ALC lymphoma associated with LyP for ALK gene products. ALK gene products were not detectable in these cases. In contrast, ALK gene products were found in a lymphonodal ALC lymphoma with subsequent extension to the skin and in t(2;5)-positive cell lines. Detection of the Epstein-Barr virus (EBV)-encoded small nuclear transcripts (EBER), and of immunoglobulin light chain transcripts served to check for the presence of cellular RNA in the tissue sections. EBER transcripts were found in scattered reactive lymphoid cells, but not in atypical or tumour cells. ALK gene expression and EBV infection seem to be a rare finding in cutaneous ALC lymphomas and LyP. This points to a molecular aetiology of primary cutaneous ALC lymphomas and LyP distinct from that of extracutaneous CD30+ lymphoproliferative disease. Detection of the t(2;5) or ALK gene products in cutaneous lymphoproliferative lesions therefore requires exclusion of extracutaneous ALC lymphoma in such patients.
Quality improvement perspective and healthcare funding decisions
Authors: A. Bloomfield
Journal: BMJ (2003)

Efforts to apply explicit prioritisation processes to healthcare funding decisions have had mixed results in New Zealand. But a quality improvement approach has advantages over existing prioritisation approaches

New Zealand, along with other countries, developed more transparency in making decisions about prioritising healthcare funding during the 1990s.1 2 In New Zealand, prioritisation approaches drew heavily on economic principles and used empirical evidence.

This paper reflects on experience with prioritisation of healthcare funding in New Zealand, identifying the benefits and also the shortcomings. It examines whether quality improvement, which is receiving increasing attention in New Zealand and internationally, is useful in making funding decisions both across and within services. We argue that a quality improvement approach has several advantages over existing prioritisation approaches, and we provide examples of how such an approach might be applied.

In the late 1980s and early 1990s, many developed countries restructured their healthcare systems, in part to improve efficiency and address rising costs. In New Zealand, major reforms in 1992 resulted in a purchaser-provider split with a strong emphasis on contracting and regulated competition. The Core Services Committee, now the National Health Committee, was established to advise the minister of health on the health service's priorities.3 A key task of the committee was to advance public debate and understanding of limited healthcare resources and the need to ration services.

The committee proposed that prioritisation decisions should be explicit and transparent and based on four principles, which have underpinned much of its subsequent work: effectiveness, efficiency, equity, and acceptability.4 Drawing on this work, a number of regional and national funding agencies developed prioritisation processes and attempted to apply these to funding allocation decisions. In 1999, the national Health Funding Authority added the principle of Maori health to those of the National Health Committee when …
Scintigraphic Detection of an Occult Abdominal Bleed in a Child
Authors: DEBRA S. MITCHELL, TERESA M. STACY, JOHN E. GRUNOW, JOE C. LEONARD
Journal: Clinical Nuclear Medicine (1988)

Although injury of the intra-abdominal viscera is less frequent than skeletal injury in the abused child, there is increasing awareness that children with injuries of the abdominal viscera may be victims of abuse. Although other modalities may accurately identify the injured organ, only angiography and radionuclide imaging have the capability to identify active bleeding sites. This case demonstrates the utilization of this technique in a child with a documented retroperitoneal hemorrhage and a duodenal hematoma.
Abstract LB-305: Novel Rac1-GEF inhibitors as anticancer agents for aggressive tumors.
Authors: Georgina A. Cardama, Nazareno Gonzalez, Maria Julieta Comin, Adrian G. Turjanski, Daniel Fernando Alonso, Daniel Eduardo Gomez, Pablo Lorenzano Menna
Journal: Cancer Research (2013)

Abstract Small GTPases of the Rho family, including Rac1, regulate fundamental cellular processes like actin cytoskeleton reorganization, cell migration and cell cycle progression. Rac1 has been associated with transformation, tumor progression and tumor cell migration in different type of cancers, including aggressive breast cancer and glioma. These proteins cycle between an active, GTP-bound state and an inactive, GDP-bound state. This cycle is highly regulated by many regulatory proteins, including activators such as guanine nucleotide exchange factors (GEFs). We searched for Rac1 inhibitors able to interfere Rac1-GEF interaction using a docking-based virtual library screening approach. We selected ZINC69391 compound. This small-molecule was able to interfere Rac-Tiam1 and Rac-DOCK180 interaction in vitro and reduced Rac1-GTP intracellular levels but had no effect on the closely related Cdc42 GTPase. ZINC69391 also affected the activation of Pak1, one important Rac1 effector. This compound reduced cell migration, inhibited cell proliferation and arrested cell cycle progression in breast cancer cells and glioma cells. We also evaluated this compound in vivo and ZINC69391 was able to reduce 60% lung colonization in a breast cancer experimental metastasis model. We further evaluated novel analogs looking for more potent and specific Rac1 inhibitors. We synthesized a group of novel disubstituted guanidines and we screened these analogs in vitro. One of them, 1A-116 analog, showed to be more potent than the parental compound, reducing cancer cell proliferation and Rac1 activation at the low micromolar range. These data further confirm Rac1 GTPase as a valuable molecular target for anti-cancer therapies and drug development in breast cancer and glioma, where Rac1 presents a relevant role. Citation Format: Georgina A. Cardama, Nazareno Gonzalez, Maria Julieta Comin, Adrian G. Turjanski, Daniel Fernando Alonso, Daniel Eduardo Gomez, Pablo Lorenzano Menna. Novel Rac1-GEF inhibitors as anticancer agents for aggressive tumors. [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 LB-305. doi:10.1158/1538-7445.AM2013-LB-305
Renal impairment, hemoglobinuria, and hemoglobinemia among patients with idiopathic thrombocytopenic purpura
Authors: Fei Xue, Chuck Wentworth, Vanitha Ganesh, Victor Gastanaga, Scott Stryker, Steven Cha, Sean Zhao
Journal: American Journal of Hematology (2011)

Renal impairment (RI) and events potentially leading to RI were reported in idiopathic thrombocytopenic purpura (ITP) patients with specific medications. This study was conducted to estimate the incidence rate (IR) of RI, hemoglobinuria and hemoglobinemia (HE) and characterize baseline risk factors in ITP and ITP-free patients. Incident ITP and matched non-ITP patients were identified from an electronic medical record database from 1990 to 2002. ITP patients were classified by the treatment first received (initiators) or ever received (users). All cohorts were followed for study outcomes. IRs were calculated and standardized by age and gender. A total of 881 ITP and 4,496 ITP-free patients yielded 3,044 and 16,006 person-years, respectively. The ITP cohort had a slightly higher prevalence of autoimmune diseases and infections than the ITP-free cohort. The IR (/10,000 person-years) for RI, hemoglobinuria and HE was 14.2, 35.7, and 7.1 in the ITP cohort; 10.0, 48.8, and 0 in the ITP-free cohort; and 18.3, 37.1, and 6.1 in untreated ITP patients, respectively. The risk of RI, HE or hemoglobinuria was not found to differ substantially between ITP and non-ITP patients or across ITP treatments.
Baffling Skin Ailments May Originate in Psyche
Authors: Lynne Lamberg
Journal: JAMA (1997)

A PATIENT brought tiny vials to the office of John Koo, MD. "Here are some of the parasites that are crawling all over me," the man told Koo, who is associate clinical professor and vice chair of dermatology at the University of California, San Francisco, School of Medicine. Koo peered into the vials. "I don't see anything," he told the patient. "Of course not," the patient retorted. "These parasites are invisible." Psychopathology plays a role in numerous skin complaints, Koo and other speakers said at the annual meetings of the American Academy of Dermatology (AAD) and the Association for Psychocutaneous Medicine of North America (APMNA) held in San Francisco in March. Such cases often prove challenging and time-consuming, speakers said, and their treatment frequently demands an inventive approach. While parasitosis is the most common delusion seen in dermatology practices, patients also seek help because they think they emit bad smells
Key workers lacked experience to deal with killer, inquiry concludes
Authors: C. Dyer
Journal: BMJ (2009)

A “systemic failure” allowed Peter Bryan, a dangerous, mentally ill killer who went on to kill two more people, to be supervised in the community by an inexperienced psychiatrist and social worker, an independent inquiry has concluded.

Mr Bryan, who has schizophrenia and has since been given a diagnosis of a personality disorder, killed an acquaintance, Brian Cherry, in 2004 and then fried and ate part of his brain. Ten days after he had been detained in Broadmoor high security hospital for the killing, he attacked a fellow inmate, Richard Loudwell, who later died of his injuries.

The reports of two separate inquiries into the two incidents, carried out for the strategic health authority NHS London, found a catalogue of failings in …
National Hockey League players' experiences with career-ending concussions
Authors: Jeffrey G Caron, Gordon A Bloom, Karen M Johnston, Catherine M Sabiston
Journal: British Journal of Sports Medicine (2013)

Objective This study investigated the experiences of National Hockey League (NHL) players who retired due to medically diagnosed concussions they incurred during their playing careers. Design An Interpretative Phenomenological Analysis (IPA; Smith et al , 2009) was used to examine the interview data. IPA is a qualitative research methodology used to understand and explore how people make sense of important life experiences and has been commonly used in health research (Smith, 2011). Setting Interviews were conducted in various cities in North America. Participants Five former NHL players whose professional careers spanned more than 10 seasons were interviewed for this project. Results Participants in this study articulated the type and intensity of the physical (eg, headaches, visual impairments) and psychological (eg, isolation, depression, suicidal ideation) concussion symptoms they endured during their careers, including how these symptoms impacted their professional careers, quality of lives, and relationships with family members and medical professionals. Participants said they continued to experience physical symptoms such as headaches, sensitivity to bright lights, and concentration problems after their careers, which has affected their post-athletic lives and has disturbed their daily functioning. Conclusions These are the first results to empirically document the experiences of professional athletes who suffered career-ending concussions. Findings from this study concur with McCrory et al 's (2009) call for longitudinal research to better understand the implications of concussive injury. Additionally, our results indicate a need for psychological counselling in conjunction with medical guidance during rehabilitation from concussion and transition to post-athletic lives. Competing interests None.
Combination of platelet fibrinogen receptor antagonist and direct thrombin inhibitor at low doses markedly improves thrombolysis.
Authors: F A Nicolini, P Lee, G Rios, K Kottke-Marchant, E J Topol
Journal: Circulation (1994)

BACKGROUND We evaluated the effects of a novel platelet fibrinogen receptor antagonist, Integrelin, and a direct thrombin inhibitor, recombinant hirudin, given together with recombinant tissue plasminogen activator (rTPA) in a canine experimental model of intracoronary thrombosis. We tested the hypothesis that combination of both agents at low doses would have an additive antithrombotic effect, resulting in a significant improvement in the efficacy of rTPA. METHODS AND RESULTS Thirty-two dogs with an electrically induced coronary thrombus were treated with rTPA (1 mg/kg over 20 minutes) together with one of the following adjunctive treatments in a random fashion. Eight dogs received saline for 90 minutes; Integrelin (5 micrograms.kg-1.min-1 for 90 minutes) was given to 8 dogs; 8 dogs received recombinant hirudin (20 micrograms.kg-1.min-1 for 90 minutes); and 8 dogs were treated with a low-dose combination of Integrelin (2.5 micrograms.kg-1.min-1) plus recombinant hirudin (10 micrograms.kg-1.min-1) for 90 minutes. Integrelin or recombinant hirudin, when given as single adjunct to rTPA, enhanced the lysis of the occlusive thrombus, causing full restoration of coronary blood flow (100% of its baseline value) for 29 +/- 16 and 26 +/- 5 minutes, respectively, whereas coronary blood flow was fully restored for only 5 +/- 1 minutes in dogs receiving rTPA plus saline (both P &lt; .05). However, either Integrelin or recombinant hirudin failed to modify the reocclusion rate (57% and 63%, respectively) compared with saline (83%; all P = NS). Conversely, the low-dose combination therapy led to complete restoration of coronary blood flow for 92 +/- 19 minutes (P &lt; .01 versus all treatments) and significantly reduced the reocclusion rate (25%; P &lt; .05 versus saline). CONCLUSIONS These data show that inhibition of specific pathways of platelet and thrombin activity improves the extent and duration of rTPA-induced thrombolysis in the electrolytic canine model. Furthermore, our findings suggest that low doses of platelet IIb/IIIa and direct thrombin antagonists in combination may be used successfully during thrombolysis.
Case 3-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Gerald Medoff, Austin L. Vickery
Journal: New England Journal of Medicine (1970)

Presentation of CaseA sixty-eight-year-old man was admitted to the hospital because of fever and a sore throat.Five days before admission he had a shaking chill, followed by fever, diaphoresis, anorexia, a severe sore throat with hoarseness, generalized aching in the bones and a cough productive of thick sputum streaked with blood. Dysphagia occurred, with anorexia, nausea and occasional retching. He was unable to walk unassisted for the three days before entry.Four years previously he had been treated at another hospital for right-sided hemiplegia and aphasia, which gradually cleared. Thereafter, he had been confined to his home. One . . .
Rheumatic Fever
Authors: Mike Sathekge, Anton Stoltz, Olivier Gheysens
Journal: Clinical Nuclear Medicine (2014)

We present a case of heterogeneous and strongly increased myocardial and valvular 18F-FDG uptake on 18F-FDG PET/CT in an HIV-positive patient with productive cough, fever, weight loss, and progressive dyspnea for 6 months. Contrast-enhanced CT did not reveal the cause of fever, but hyperechogenic valvular lesions on echocardiography in combination with PET/CT findings are suggestive of endocarditis/myocarditis. Postmortem histology 3 weeks after PET/CT showed Aschoff bodies with Anitschkow cells, pathognomonic for rheumatic carditis. This case illustrates that rheumatic heart disease can be detected on 18F-FDG PET/CT and demonstrates the value of 18F-FDG PET/CT in patients with fever of unknown origin.
CONTACT ECZEMA DUE TO CLOTHING
Authors: Frank A. Simon
Journal: JAMA (1934)

Eczema due to contact with various substances in the environment is a well recognized condition to which the literature contains many references.1 The diagnosis of the cause in the individual patient is not easy, and the case reported here demonstrates the need of prolonged study and observation and the good results that will reward the effort. It also shows how widely distributed the cause of trouble may be. <h3>REPORT OF CASE</h3> A man, aged 29, developed a small area of eczema on the left wrist in November, 1928. Similar lesions soon appeared on the dorsal aspect of both hands and fingers. They were of the acute, vesicular type, with oozing and thickening of the skin. It is of interest to note that the lesions made their first appearance at the site of an abrasion caused by a stiffly starched cuff. Various local applications had no apparent effect on the course
Abstract 952: The SCF F box protein, Skp2, is a key component of an E3 ubiqutin ligase that governs estrogen receptor ≤ stability
Authors: Wen Zhou, Jun Sun, Joyce M. Slingerland
Journal: Cancer Research (2012)

Abstract Breast carcinoma is the most common cancer among women in developed countries, and about 70% of these tumors express estrogen receptor ≤ (ERα). ERα is a transcription factor and master regulator of estrogen stimulated proliferation and its expression indicates potential for response to estrogenic stimulation. A majority of ERα positive breast cancers initially respond well to selective estrogen receptor modulators (such as tamoxifen) or to aromatase inhibitors. Understanding the regulation of ERα levels and its role in transcription of estrogen driven genes is thus highy germane to breast cancer therapy. There is evidence that for many transcription factors, activation is linked to factor degradation. Moreover, estrogen stimulation is known to activate ERα proteolysis. Given the importance of estrogen as a driver of breast cancer progression, we have investigated mechanisms governing ERα proteolysis. S phase kinase-associated protein 2 (Skp2) is an F box component of a multi-protein SCF ubiquitin ligase that acts on multiple substrates. Levels of Skp2 have been reported to be inversely related with the levels of ERα in breast cancer. Here we report that SCFSkp2, comprised of Skp2, in association with Skp1, Cul1 and Rbx1, is an E3 ubiquitin ligase for ERα. Ectopic expression of dominant negative Cul1 increases ERα levels by impeding ERα degradation in breast cancer cells. Knockdown of Skp2 impairs estrogen-triggered ERα proteolysis, while ectopic Skp2 expression decreased ERα stability. We show that Skp2, Skp1, Rbx1 and Cul1 co-precipitate with cellular ERα and the formation of this ERα/SCFSkp2 complex is cell cycle regulated and parallels CDK2 activation. We also show ER is an in vitro substrate that is ubiquitylated and degraded by SCFSkp2. The involvement of CDK2-dependent ERα phosphorylation in estrogen activated ERα/SCFSkp2 binding, ERα proteolysis and the functional consequences of this on ERα transcriptional activity are under investigation. These data suggest that Skp2 plays an important role in the regulation of ERα stability, and potentially in the biologic action of this key steroid hormone receptor in breast cancer. 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 952. doi:1538-7445.AM2012-952
Clinical Use of a Nomogram to Estimate Proper Ventilation during Artificial Respiration
Authors: Edward P. Radford, Benjamin G. Ferris, Bertrand C. Kriete
Journal: New England Journal of Medicine (1954)

WHEN a patient is unable to breathe by himself, the single most important responsibility of the physician is to provide adequate ventilation of the lungs. Artificial respiration during anesthesia may be required for several hours, and the treatment of respiratory paralysis in poliomyelitis may be necessary for much longer periods. Under these conditions the physician must consider any deviations from proper ventilatory levels in the light of their long-term effects.The first concern of the physician giving artificial respiration is to maintain oxygenation of the patient's arterial blood. Often, he does this by providing high concentrations of oxygen in the . . .
Bilateral nail dystrophy associated with vibrating tool use
Authors: V.C. Diba, S.A. Holme, R. Savage, C.M. Mills
Journal: British Journal of Dermatology (2003)

Sir, We report a 68‐year‐old man who presented with an 18‐month history of paraesthesia affecting the radial three digits of both hands. This was associated with abnormal growth and appearance of the index and middle fingernails. He had no specific past medical history and was not taking any medication. He had worked as a labourer for an electricity company for 30 years using drilling tools to break tarmac to allow the laying of cables. Examination revealed wasting of the thenar eminence of both hands with reduced power of thumb flexion (Fig. 1a). There was decreased light touch sensation affecting the index and middle fingers, and Tinel's sign was positive bilaterally. Nail dystrophy in the corresponding area was evident with subungual hyperkeratosis of the left middle fingernail, and thickening of the right index and middle fingernails (Fig. 1b). Blood investigations were unremarkable and there was no evidence of fungal elements on mycological examination of nail clippings. A diagnosis of carpal tunnel syndrome (CTS) with secondary nail dystrophy to was felt to be in keeping with the clinical findings. He is currently awaiting nerve conduction investigations, although it is felt that nerve decompression is unlikely to improve his symptoms due to his late presentation and age.