tbuckley/cabot-search huggingface dataset:
Talking about drug treatments
Authors: T Greenhalgh
Journal: BMJ (1994)

Most of our professional lives are conducted within spitting distance of a computer. Rote learning of large amounts of information is an obsolete skill, replaced in some of us by the ability to assess the relevant database on the appropriate machine. The term “data protection” generally refers to an individual's right to see and amend computer held information about himself or herself. But neither the law nor any other mechanism can yet protect us from the mountains of data which fall unsolicited into our hands everywhere from the supermarket checkout to our own front doormats. In the age of the fax, the modem, and high technology …
The prevention of titanium-particle-induced osteolysis by OA-14 through the suppression of the p38 signaling pathway and inhibition of osteoclastogenesis
Authors: Bo Tian, Tao Jiang, Zhanying Shao, Zanjing Zhai, Haowei Li, Qiming Fan, Xuqiang Liu, Zhengxiao Ouyang, Tingting Tang, Qing Jiang, Minghao Zheng, Kerong Dai, An Qin, Yongping Yu, Zhenan Zhu
Journal: Biomaterials (2014)
Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display.
Authors: D Rajotte, W Arap, M Hagedorn, E Koivunen, R Pasqualini, E Ruoslahti
Journal: Journal of Clinical Investigation (1998)

Vascular beds are known to differ in structure and metabolic function, but less is known about their molecular diversity. We have studied organ-specific molecular differences of the endothelium in various tissues by using in vivo screening of peptide libraries expressed on the surface of a bacteriophage. We report here that targeting of a large number of tissues with this method yielded, in each case, phage that homed selectively to the targeted organ. Different peptide motifs were recovered from each of these tissues. The enrichment in homing to the target organs relative to an unselected phage was 3-35-fold. Peptide sequences that conferred selective phage homing to the vasculature of lung, skin, and pancreas were characterized in detail. Immunohistochemistry showed that the phage localized in the blood vessels of their target organ. When tested, the phage homing was blocked in the presence of the cognate peptide. By targeting several tissues and by showing that specific homing could be achieved in each case, we provide evidence that organ- and tissue-specific molecular heterogeneity of the vasculature is a general, perhaps even universal, phenomenon. Our results also show that these molecular differences can serve as molecular addresses.
Viewing the body after bereavement due to a traumatic death: qualitative study in the UK
Authors: A. Chapple, S. Ziebland
Journal: BMJ (2010)

Objective Whether bereaved relatives should be encouraged to view the body after a traumatic death is uncertain. This analysis of narrative interviews interprets people's accounts of why and how they decided whether to view the body and their emotional reactions to this, immediately and at a later stage. Design In depth interviews with qualitative analysis. Participants A maximum variation sample of 80 people bereaved because of suicide or other traumatic death. Setting Most people were interviewed in their homes. Results For those who had the option, decisions about seeing the body varied. Some wanted someone else to identify the body, because they feared how it might look or preferred to remember their relative as they had been in life. Those who had wanted to see the body gave various reasons beyond the need to check identity. Some felt they ought to see the body. Others felt that the body had not lost its social identity, so wanted to make sure the loved one was "being cared for" or to say goodbye. Some people wanted to touch the body, in privacy, but the coroner sometimes allowed this only after the postmortem examination, which made relatives feel that the body had become police property. Seeing the body brought home the reality of death; it could be shocking or distressing, but, in this sample, few who did so said they regretted it. Conclusions Even after a traumatic death, relatives should have the opportunity to view the body, and time to decide which family member, if any, should identify remains. Officials should prepare relatives for what they might see, and explain any legal reasons why the body cannot be touched. Guidelines for professional practice must be sensitive to the needs and preferences of people bereaved by traumatic death. The way that relatives refer to the body can be a strong indication for professionals about whether the person who died retains a social identity for the bereaved.
P17.67 * SUBCUTANEOUS METASTASES FROM A GLIOBLASTOMA MULTIFORME: CASE REPORT AND REVIEW OF LITERATURE
Authors: J. Perez, J. Fernandez, T. Ribas, P. Barrio, A. Mostaza
Journal: Neuro-Oncology (2014)

OBJECTIVES: We expose the case of a long-survival glioblastoma multiforme (‘GBM’) located at posterior fossa which presented a subcutaneous metastases four years after the surgery without evidence of recurrence throughout Central Nervous System (‘CNS’) previous at the secondary diagnosis. METHODS: A 57-year-old came to the Emergency Department with vomits, instability and pulsating headache. The neurological exploration showed posterior fossa signs and the Magnetic Resonance Image (MRI) confirmed a mass located on the right cerebellum hemisphere, with radiological characteristic of high-grade glioma, without associated hydrocephalus. A total gross resection was performed, being forced to return to the operating room due to a post-operative hematoma. After that, the clinical evolution was satisfactory and the patient could receive adjuvant treatments, finishing them with a Karnofsky Performance Status of 80. After four years of progression-free survival, we observed a stiff and painful area over the scar that was completely removed. Confirmed the ‘GBM’ diagnosis, the patient received chemotherapy without good response and, after five years of overall survival and one year after the second diagnosis, the patient died due to a neural and systemic tumoral progression. RESULTS: The cerebellar lesion met the anatomopathological criteria to be diagnosed as a ‘GBM’: cellular atypia, mitosis, endovascular proliferation and necrosis, with an extent oligodendroglial component. For this reason, we made the test for 1p/19q codeletion, which was negative. The subcutaneous tumor could be diagnosed as a ‘GBM’ metastases by cytomorphology and the similar immunohistochemical results between both samples. There was a positive GFAP cellular proliferation with a MIB-1 index about 20%. Since 2002, nine cases of confirmed subcutaneous metastases of 'GBM' have been reported, but their overall survival were shorter than this case, maybe because of the important oligodendroglial component and the infratentorial location of the primary lesion in this patient. CONCLUSIONS: Due to the extreme aggressiveness and the natural history of ‘GBM’, the incidence of metastases is very low and its appearance in the subcutaneous tissue is exceptional. Because of their low incidence and the short survival of these patients, the subcutaneous metastases are often misdiagnosed as primary subcutaneous tumors. There is a strong relationship between metastases and invasive procedures, like craneotomies and the placement of Ommaya reservories or ventricular drainages. The clinical history and, specially, the anatomopathological and immunohistochemical results of both lesions are essential for the correct diagnosis.
Racemic Warfarin and Trimethoprim-Sulfamethoxazole Interaction in Humans
Authors: ROBERT A. O'REILLY
Journal: Annals of Internal Medicine (1979)

Eleven normal humans were studied to evaluate the reported interaction of racemic sodium warfarin and trimethoprim-sulfamethoxazole prospectively. Single oral doses of racemic warfarin, 1.5 mg/kg of body weight, were administered with and without 320 mg of trimethoprim and 1600 mg of sulfamethoxazole orally, beginning 7 d before the warfarin and continuing daily throughout the hypoprothrombinemia. Daily plasma samples were analyzed for one-stage prothrombin activity (Quick) and for warfarin content by high-pressure liquid chromatography. Transient cutaneous reactions developed in four of 11 subjects: a morbilliform rash in three (studies discontinued) and generalized pruritus in one. A highly significant augmentation of the warfarin effect on the mean one-stage prothrombin activity (P < 0.003) occurred with trimethoprim-sulfamethoxazole, but no significant effect was found on the warfarin half-life (P > 0.5). It is concluded that trimethoprim-sulfamethoxazole interacts with racemic warfarin, possibly at a receptor-site locus.
Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia
Authors: Neil P. Shah, John M. Nicoll, Bhushan Nagar, Mercedes E. Gorre, Ronald L. Paquette, John Kuriyan, Charles L. Sawyers
Journal: Cancer Cell (2002)
Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis
Authors: R. G. Crystal, N. G. Mcelvaney, M. A. Rosenfeld, Chin-Shyan Chu, A. Mastrangeli, J. G. Hay, S. L. Brody, H. A. Jaffe, N. T. Eissa, C. Danel
Journal: Nature Genetics (1994)
Abstract 4890: Periostin signaling regulates breast cancer stem cells.
Authors: Arthur W. Lambert, Sait Ozturk, Panos Papageorgis, Hamid Abdolmaleky, Sam Thiagalingam
Journal: Cancer Research (2013)

Abstract Recent evidence suggests that the molecular heterogeneity inherent to breast cancer, which underlies metastasis, resistance to treatment and disease recurrence, can be driven by a distinct subpopulation of tumor cells referred to as cancer stem cells (CSCs). However, the extracellular cues and intracellular pathways that CSCs rely on remain unclear. Working with a breast cancer progression model system we found the invasive breast cancer cell line to exhibit numerous stem-like characteristics. Gene expression profiling, along with a careful review of the literature, identified a secreted extracellular matrix molecule, periostin (POSTN), which we hypothesized to be required for the maintenance of a cancer stem cell state. POSTN expression was increased in numerous basal-like breast cancer cell lines that contain an expanded CSC population, as well as in cells grown as mammospheres and in the CD44+/CD24- fraction of tumor cells. Furthermore, CSC-like lines displayed increased surface levels of the alpha-v beta-3 integrin heterodimer, a known receptor for POSTN, suggesting that hyperactivation of a POSTN signaling axis could potentially regulate the CSC state. Using stable cell lines expressing an shRNA directed at POSTN we have found that POSTN is required for efficient mammosphere formation and for the maintenance of an ALDH-positive CSC population. In line with this, we found these cells had impaired Erk and Wnt signaling and expressed less IL-6 and IL-8, known regulators of CSCs. Furthermore, high POSTN expression correlates with a worse clinical prognosis in basal-like breast cancer patients. Therefore, we suggest that POSTN signaling through integrin receptors may enrich for highly tumorigenic breast CSCs in a subset of basal-like tumors, leading to aggressive and recurrent malignancies. More broadly, our results imply that a supportive tumor niche can be established and maintained by cancer cells, and raises the possibility of targeting components of this extracellular environment to eradicate breast CSCs. Citation Format: Arthur W. Lambert, Sait Ozturk, Panos Papageorgis, Hamid Abdolmaleky, Sam Thiagalingam. Periostin signaling regulates breast cancer stem cells. [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 4890. doi:10.1158/1538-7445.AM2013-4890
The Doctor's Letter of Condolence
Authors: S E Bedell, K Cadenhead, T B Graboys
Journal: New England Journal of Medicine (2001)

In response to an article on grief, one of us received the following letter (the names have been changed):Dear Doctor,On August 3, my mother, Jean Smith, died. She had been a patient at the Medical Center with Dr. Roberts. Until her death, at 90, she was an active person, involved with her family and the world — driving, going to yoga class. She died suddenly, in her sleep. We are all bereft.Several weeks after her death, I wrote to Dr. Roberts to tell him that she had died. I told him how very much I appreciated his . . .
COMPARATIVE BIOCHEMICAL STUDIES ON NORMAL AND ON POLIOMYELITIS VIRUS-INFECTED TISSUE CULTURES
Authors: Ernest Kovacs
Journal: The Journal of Experimental Medicine (1956)

Experimental evidence is presented for drastic changes in phosphomonoesterase activities of tissue cultures, brought about by infection with poliomyelitis viruses. Acid phosphatase activity went through a maximum before decreasing almost to zero level. Alkaline phosphatase activity diminished progressively to zero, then with disruption of the cells attamed normal levels. Various aspects of the kinetics were investigated and illustrated. The initial increase of acid phosphatase, in contrast with the alkaline, may mean that the reactions catalyzed by this enzyme continue during the early phase. This period is the time of intense virus production and therefore it was supposed that this enzyme may play some role in virus synthesis. It was assumed that the virus acts as a particle of molecular size and becomes associated with the enzyme complex physicochemically or chemically. This association ends with the disintegration of the host cells. During the cell-virus interaction a toxin may develop which is a strong and general enzyme inhibitor. Various enzyme systems differ in sensitivity toward these virus effects; for instance, acid phosphatase is irreversibly inhibited or may be destroyed. The visible CPE of virus is preceded by a drastic reduction of enzyme activities in whole TC and in its various fractions, which may suggest causal relationship in the mechanism of cell destruction. In arrested or latent infection these processes are operative, but on a smaller scale. The drop in activities cannot be explained by the reduction of tissue mass, which is the consequence, rather than the cause, of enzyme changes. Besides the theoretical significance of these observations the following practical points can be summarized: 1. Changes in phosphatase activities are most strikingly demonstrated in whole tissue cultures inoculated with poliomyelitis virus. 2. There is causal relationship among infection, enzyme changes, and transformation of cell physiology. 3. The biochemical approach provides a quantitative measure of the extent of cell damage, before visible CPE is detectible. 4. Unapparent and active infections with poliomyelitis virus could be differentiated from normal controls by this method. 5. By various manipulations (freezing, long incubation) the difference between normal and infected TC can be enhanced. Suitable technical methods were proposed for various types of investigations.
Different expression of adhesion molecules and tetraspanins of monocytes of patients with atopic eczema
Authors: J. J. Jockers, N. Novak
Journal: Allergy (2006)

Background: Atopic eczema (AE) and psoriasis vulgaris (Pso) represent the most frequent chronic inflammatory skin diseases, which have a high number of characteristics in common but differ in their clinical picture and immunological background. A shared feature of both AE and Pso is a high recruitment of distinct proinflammatory cells from the blood into the skin at the initiation of the disease. A multistep adhesion cascade via different adhesion receptors consisting of ‘tethering’ and ‘rolling’ mediated by selectins, α ‐integrins and β ‐integrins and the ‘arrest’ of the cells is initiated during this process. Aims of the study: To evaluate the expression of adhesion molecules and tetraspanins of monocytes of patients with AE and Pso in comparison with healthy controls. Methods: We analysed the expression of adhesion molecules and tetraspanins on monocytes freshly isolated from the peripheral blood of patients with AE ( n = 40) and Pso ( n = 65) during exacerbation of their disease in comparison with healthy, non‐atopic controls ( n = 50). Results: A high number of similarities between monocytes of patients with AE and patients with Pso, and disease‐related differences in the expression of CD62L, CD62P, CD11a, CD11b, CD11c, CD49b, CD49d, CD49e and CD18 and the tetraspanins CD9, CD53, CD63 and CD151, which were elevated on monocytes of patients with AE could be observed. Conclusion: A distinct expression pattern of adhesion molecules and tetraspanins on monocytes of patients with AE and Pso might influence the recruitment process of inflammatory precursor cells and facilitate new approaches for therapeutic strategies aimed at interrupting the very earliest steps of the fateful recruitment process.
TLR4 inactivation protects from graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
Authors: Yi Zhao, Qiuyan Liu, Li Yang, Donghua He, Lijuan Wang, Jun Tian, Yi Li, Fuming Zi, Hanying Bao, Yang Yang, Yuanyuan Zheng, Jimin Shi, Xingkui Xue, Zhen Cai
Journal: Cellular and Molecular Immunology (2012)
Rethinking Consultants: Time for change in traditional working practices?
Authors: J. Bailey
Journal: BMJ (1995)

Consultants in Britain are under pressure to change the way they organise their work. Many rely on formal, but unwritten, rules and a culture of "learning by doing." Unlike their counterparts in Sweden, they are often not well integrated into the management systems of their hospitals. The result is wide differences in the NHS workloads of individual consultants and, for a minority, conflicts of interest with their private work. The training received by junior doctors varies because it is largely left to individual consultants. Clinical directorates should provide a more effective mechanism for consultants to influence trust policies and for consultants to implement these policies. Consultants must not only recognise the need for change but also seize the initiative.
Treating the Polycystic Ovary Syndrome the Old-Fashioned Way
Authors: David S. Guzick
Journal: New England Journal of Medicine (2007)

Of the estimated 6.7 million women with fertility problems in the United States, 35% have received drugs to induce ovulation.1 The most common cause of anovulation among infertile women is the polycystic ovary syndrome, a condition typically characterized by irregular menses, androgen excess, and polycystic-appearing ovaries. The condition is associated with insulin resistance and obesity.Although a number of drugs have been used to induce ovulation in women with the polycystic ovary syndrome, clomiphene citrate is a simple, tried-and-true treatment. Clomiphene is an orally active, antiestrogenic substance that promotes the release of follicle-stimulating hormone from the pituitary gland, thus stimulating . . .
Chemical genomics: Functional analysis of orphan nuclear receptors in the regulation of bile acid metabolism
Authors: Timothy M. Willson, Stacey A. Jones, John T. Moore, Steven A. Kliewer
Journal: Medicinal Research Reviews (2001)

Abstract Chemical genomics is the name we have given to the analysis of gene function through use of small molecule chemical tools. Orphan nuclear receptors are ideally suited to this technique of functional analysis, since their activity as transcription factors is regulated by small hydrophobic ligands. GW4064 is a potent and selective nonsteroidal ligand for the nuclear bile acid receptor FXR (NR1H4). Using GW4064 as a chemical tool, we have identified genes regulated by FXR in the liver, including those involved in bile acid synthesis and transport. We have also discovered that PXR (NR1I2) is a lithocholic acid receptor that controls the biosynthesis and metabolism of bile acids. Together FXR and PXR cooperate to control biliary and urinary bile acid excretion. These functions suggest that potent PXR and FXR ligands may offer a new approach to the treatment of cholestatic liver disease. © 2001 John Wiley &amp; Sons, Inc. Med Res Rev, 21, No. 6, 513–522, 2001
Surgery in the Hemophiliac
Authors: Oscar D. Ratnoff
Journal: JAMA (1968)

The extraordinary number of books concerning the hereditary hemorrhagic disorders continues to increase, reflecting an interest out of proportion to the number of afflicted individuals. When Tarnay's<i>Surgery in the Hemophiliac</i>appeared in the mail, my first reaction was, "Not another." Happily, this short monograph turns out to fill a need. Tarnay deals explicitly with the therapy of many surgical problems in the hemophiliac, bolstering his text heavily with references to the published literature. His recommendations are specific, and chiefly unexceptionable. This reviewer does not share Tarnay's enthusiasm for the use of epsilon aminocaproic acid. Repeated double-blind studies have demonstrated the inefficacy of this drug except for the control of hematuria. In this situation, its use has been followed by ureteral obstruction and hydronephrosis. Further, prolonged prophylactic use has been complicated by prostatitis. Tarnay's recommendation, then, that administration of epsilon aminocaproic acid in sufficient dosage should "accompany any hospitalization for
Ethical Implications of Rejecting Patients for Clinical Trials
Authors: Henry G. Bone
Journal: JAMA (1990)

<h3>To the Editor.—</h3> I take strong exception to certain editorial comments of Dr Chalmers<sup>1</sup>on the ethics of exclusion of patients from clinical trials. He seems to misunderstand the fundamental purpose of the clinical trial, which is to<i>evaluate</i>therapy, not to provide it to all and sundry. No patient has a<i>right</i>to be included in a clinical trial. The investigator's principal obligation is to answer the questions at hand; otherwise, no trial should be conducted. The inclusion of subjects who cannot properly be evaluated because of confounding variables may obscure important results and require an excessive number of subjects to be exposed to a treatment to overcome the "noise." The exposure of the subjects to a potentially harmful treatment thus may be "wasted." This is a real ethical error. If the trial is necessary in the first place, it is essential that it be conducted in the
Treatment of two patients with generalized pustular psoriasis with the interleukin-1β inhibitor gevokizumab
Authors: B. Mansouri, L. Richards, A. Menter
Journal: British Journal of Dermatology (2014)

Generalized pustular psoriasis (GPP) is a severe, potentially life-threatening inflammatory dermatosis, which is traditionally difficult to manage. Recent evidence suggests that interleukin (IL)-1 plays a central role in the disease pathogenesis, and thus makes the use of IL-1 inhibitors potentially effective. Two patients with severe, recalcitrant GPP were enrolled in an open-label, expanded access study to receive a new IL-1β inhibitor, gevokizumab. The two patients had a respective 79% and 65% reduction in GPP area and severity index scores at weeks 4 and 12, with some improvements in quality-of-life instruments. There were no significant adverse events related to the study medication, although one patient developed an abscess in a haematoma secondary to an injury. Both patients showed substantial initial clinical response to gevokizumab, with no significant laboratory abnormalities noted. These cases illustrate the growing need for targeted, efficacious therapies for this severe, debilitating disease. Prospective randomized control studies are required to further assess the safety and efficacy of IL-1β inhibitors for the treatment of GPP.
Localization of a Parathyroid by 131I Scintiscan
Authors: James A. Mailliard
Journal: JAMA (1968)

A significant number of patients with hyperparathyroidism have palpable thyromegaly. In a man with "goiter" and clinical hyperparathyroidism, a cystic parathyroid adenoma was delineated by thyroid scintiscan. The I<sup>131</sup>thyroid scan may be a valuable adjunct in the evaluation of hyperparathyroidism.