tbuckley/cabot-search huggingface dataset:
Abstract 1760: Development of bisphosphonate prodrugs of doxorubicin for targeting bone metastases that are cleaved pH dependently or by cathepsin B
Authors: Katrin Hochdörffer, Cynthia Schäfer-Obodozie, Christoph Schächtele, Felix Kratz
Journal: Cancer Research (2012)

Abstract Bone metastases occur in up to 80 % of patients with advanced breast or prostate cancer and significantly affect the quality of life. Most frequently, bone metastases cause bone fractures, severe pain and hypercalcaemia. Current options for treating of bone metastases are surgery, radiotherapy, chemotherapy, hormone therapy, and the administration of bisphosphonates. These treatments are primarily palliative and can improve the quality of life in some cases, however without increasing the survival time of the patients. Bisphosphonates are presently the most active inhibitors of bone degradation, and they can reduce bone pain, bone destruction and tumor growth. Their therapeutic effects are due to the high affinity between bisphosphonates and the apatite structure of bone and bone metastases. In order to improve the outcome of treating bone metastases, new therapeutic approaches are urgently required. As bone-seeking agents, bisphosphonates show an uptake in the bone of 20-60% of the applied dose, and in general the uptake in bone metastases is 10-20-fold higher than in healthy bone tissue. In addition, bone metastases are characterized by an acidic pH and the over-expression of several proteases including cathepsins, matrix metalloproteases, plasmin and uPA. Surprisingly, no prodrug approaches have been reported to date that exploit the bone targeting effect of low-molecular weight bisphosphonates with a concomitant release of a bound drug in bone metastases. To this purpose, we developed water-soluble bisphosphonate prodrugs of doxorubicin for targeting bone metastases by conjugating a thiol-bearing aliphatic bisphosphonate with the 6-maleimidocaproyl hydrazone derivative of doxorubicin (1) that is cleaved pH dependently, or by attaching a maleimide derivative of the dipeptide Val-Ala-PABC (PABC = p-benzyloxycarbonyl) to the aliphatic bisphosphonate (2). Incubation studies with cathepsin B and 2 at 37 °C showed a cleavage of doxorubicin after two hours with a half time of ∼ 45 min and 1 released doxorubicin quantitatively at pH 5.0 after 2 h. The plasma stabilities (human and mouse) of both prodrugs were in the range of 3-6 h at 37 °C. Binding studies of 1 and 2 with a major component of bone, i.e. hydroxyapatite, demonstrated binding of 80-90 % of both prodrugs after 4 h at 37 °C. Finally, in an orientating toxicity study in nude mice the maximum tolerated dose (MTD) of 1 was three-fold higher compared to conventional doxorubicin whereas 2 showed essentially the same MTD as doxorubicin. 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 1760. doi:1538-7445.AM2012-1760
Mutations in the hepatitis B virus precore/core gene and core promoter in patients with severe recurrent disease following liver transplantation
Authors: J S McMillan, D S Bowden, P W Angus, G W McCaughan, S A Locarnini
Journal: Hepatology (1996)

Recurrent hepatitis B virus (HBV) infection is a major problem in patients undergoing liver transplantation. Previously, we reported that infection with HBV strains containing a mutation in the precore region (G-to-A at nucleotide 1896) was associated with severe recurrent disease posttransplantation. In this study we investigated other mutations in the precore/core gene and core promoter which may be associated with this severe recurrence. The precore/core gene and core promoter of HBV from pre and posttransplantation sera of 15 patients with HBV recurrence were amplified by polymerase chain reaction (PCR) and sequenced. Pre and posttransplant sequences were very similar for each patient. HBV from patients who developed severe recurrence had significantly more mutations in both the nucleotide (P < .05) and predicted amino acid (P < .05) sequences of the precore/core gene, but not in the core promoter, than virus from patients with mild recurrence. There was also an apparent link between severe disease and HBV strains of genotype D (P < .05). The number of nucleotide and amino acid mutations in the precore/core gene was strongly associated with the presence of the precore mutation (P < .01). Mutations were found throughout the entire gene, however, at the amino acid level clustering was observed in the B- and helper T-cell epitopes as well as nuclear localization signals. In the encapsidation signal, nucleotide mutations were found that were predicted to increase the stability of the stem-loop structure. Overall, our data shows that genotype D and accumulated mutations throughout the HBV precore/core gene, but not core promoter, were associated with severe recurrent disease posttransplantation. These mutations were strongly linked to the presence of the precore mutation at nucleotide position 1896 and may contribute to the poor outcome in these patients.
Diseases of the alimentary system; Nausea and vomiting.
Authors: D Gibbs
Journal: BMJ (1976)

disappointed with a radical approach and now palliate initially and aim to correct at about the age of 5 years.If early correction is contemplated in certain conditions in which palliation is not so helpful, not only must the anatomical diagnosis be exact, but the patients must be in as good a clinical state as possible pre- operatively.In this respect, early referral of these sick infants and careful maintenance of the acid base state are vital. CONCLUSIONWe have attempted to record the performance of a regional unit dealing with a full range of cardiac disease.Full back-up is necessary from biochemical, haematological, and radiological services, from the physiotherapy department, and from the blood bank, but the organisation of the unit is simple and does not need much technical support.The unit does not use large amounts of homologous blood.Although this sttldy was not designed to show long-term results, our own experience is confirming the results of others that the obvious early benefit is sustained in most patients as time goes on.Necessarily the cost per patient is high when compared with simpler surgical procedures but it is probably fairer to compare the expense we incur with the overall cost of treating other life-threatening or disabling diseases if such comparisons have to be made.In terms of symptomatic relief, return to a useful and productive life, decreased dependence on others, and, in children, the improved prospects for the future, including normality at school, we believe that we are showing that the expense is justified and is a sound and proper use of resources.We thank the members of the junior medical staff, nursing staff, technicians, laboratory staff, and many others who have contributed so much to the running ofthis unit during the period covered by this report.
Effect of luminal ions on the transepithelial electrical potential difference of human rectum
Authors: E. Q. Archampong, C. J. Edmonds
Journal: Gut (1972)

Skin electrodes are the most convenient reference electrodes for clinical measurements of electrical potential differences (pd) across the epithelium of the alimentary tract but the presence of an electrical charge on normal skin introduces an error. In the present study, by comparison with results obtained using subcutaneous and intravenous electrodes, it was shown that an intradermal injection of saline abolished the skin potential differences. This simple method, therefore, allows skin electrodes to be used to measure the true transepithelial potential differences of gut mucosa. The method was applied to investigate the effect on the rectal potential difference of altering the composition of the luminal solutions. Changes in the cations (sodium, potassium, magnesium) showed that sodium was the most important cationic determinant of the potential difference, especially when sodium absorption was stimulated by giving mineralocorticoids. Changes in the anions (chloride, iodide, bromide, nitrate, bicarbonate, sulphate, phosphate, citrate, and acetate) indicated that the molecular size of the anion rather than its chemical nature was the significant factor and suggested that the ions had to cross a barrier relatively impermeable to anions of radius greater than 3·5 to 4 A°. Changes in osmolality and glucose concentration were without effect.
Abstract 5381: A novel strategy to eliminate chemoresistant colon cancer cells
Authors: Shailender S. Kanwar, Yingjie Yu, Jyoti Nautiyal, Bhaumik B. Patel, Subhash Padhye, Fazlul H. Sarkar, Adhip P.N. Majumdar
Journal: Cancer Research (2011)

Abstract Recurrence of colon cancer, which affects nearly 50% of patients treated by conventional therapeutics, is thought to be due to re-emergence of chemotherapy-resistant cancer stem/stem-like cells (CSCs) Therefore, development of therapeutic strategies for targeted elimination of CSCs would be a novel treatment strategy for colon cancer. The current study examines whether diflourinated-curcumin (CDF), a novel analog of the dietary ingredient of curcumin, in combination with 5-fluorouracil and oxaliplatin (5-FU+Ox), the mainstay of colon cancer chemotherapeutic, would be an effective strategy to eliminate colon CSCs. Multiple molecular techniques that include real-time RT-PCR, Western blot analysis, MTT assay, caspase-3 activity, colonosphere formation in stem cell media, Hoechst-33342 dye exclusion and NF-κB-ELISA, were used. We observed that CDF together with 5-FU+Ox to be more potent than curcumin in reducing CD44 and CD166 expression. This was accompanied by inhibition of cell growth, induction of apoptosis and disintegration of colonospheres. These changes were associated with down-regulation of the membrane transporter protein ABCG2, and attenuation of EGFR, IGF-1R, and NF-κB signaling consistent with inactivation of β-catenin, COX-2, c-Myc and Bcl-xL and activation of the pro-apoptotic Bax. Our results suggest that CDF together with the conventional chemotherapeutics could be an effective treatment strategy for preventing the emergence of chemo-resistant colon cancer cells by eliminating CSCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5381. doi:10.1158/1538-7445.AM2011-5381
Bone marrow-derived progenitor cells develop into myeloid-derived suppressor cells at metastatic sites
Authors: Amber Giles, Yorleny Vicioso, Miki Kasai, Steven Highfill, Arnulfo Mendoza, Rosandra Kaplan
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts The ability of tumor cells to metastasize to distant tissues is the most lethal aspect of cancer. Prior to detectable metastasis tumors elicit distant changes within the bone marrow and future sites of metastasis, including formation of the pre-metastatic niche. We have found that
WSX-1 Is Required for the Initiation of Th1 Responses and Resistance to L. major Infection
Authors: Hiroki Yoshida, Shinjiro Hamano, Giorgio Senaldi, Todd Covey, Raffaella Faggioni, Sharon Mu, Min Xia, Andrew C Wakeham, Hiroshi Nishina, Julia Potter, Chris J.M Saris, Tak W Mak
Journal: Immunity (2001)
End-Stage Renal Disease Therapy
Authors: Eli A. Friedman
Journal: JAMA (1996)

<h3>Continuation of the US Kidney Program Is the Issue</h3> Congress, the president, and organized medicine are currently assessing all aspects of government expenditures for health care. Previous constraints on reducing funding for Medicare have yielded under the pressure of the announcement by Medicare's trustees that unless curtailed, Medicare will be bankrupt shortly after the turn of the century (2002).<sup>1</sup>By law, once the Medicare fund is exhausted, no payments for hospital or any other trust-paid services may be made. I fear this threat to America's pioneer program that since 1973 has treated all citizens afflicted with end-stage renal disease (ESRD). In 1992, more than 205 000 patients were treated for ESRD in the United States with an unadjusted acceptance rate of 212 per million and a point prevalence rate on December 31, 1992, of 794 per million.<sup>2</sup>Superficial inspection of the Medicare ESRD program indicates to some that costs
Physical Medicine and Rehabilitation
Authors: Kristi L. Kirschner
Journal: JAMA (1993)

Physiatry has continued to evolve with changing patterns of illness and disability. The Institute of Medicine estimates that 35 million Americans (approximately one in seven) have disabling conditions.<sup>1</sup>More than 9 million are unable to work, study, or live independently. The average American will live almost 13 years with some sort of limitation. A 1988 National Health Interview Study showed that the incidence of disability increases dramatically with age.<sup>2</sup>About 5% of those under the age of 18 years have some degree of activity limitation, increasing to almost 40% in those 65 and over. Chronic illnesses, arthritis, strokes, trauma, and pain syndromes account for a significant proportion of functional limitations. As specialists in the pathogenesis, prevention, and remediation of disability, physiatrists are in a position to assist a variety of practitioners in maximizing function and quality of life. In particular, there have been exciting advances in the treatment
Review: Statins do not increase minor or serious symptomatic adverse events in placebo-controlled trials
Authors: Meera Jain, Richard Wernick
Journal: Annals of Internal Medicine (2014)

Source Citation Finegold JA, Manisty CH, Goldacre B, Barron AJ, Francis DP. What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice. Eur J Prev Cardiol. 2014;21:464-74. 24623264
“Serum B<sub>12</sub>” and the Diagnosis of Cobalamin Deficiency
Authors: Robert M. Donaldson
Journal: New England Journal of Medicine (1978)

Two papers in this issue of the Journal will surely give pause to physicians who by and large have come to expect that a routinely ordered "serum B12" will automatically tell them whether a patient is cobalamin deficient. Cooper and Whitehead report that serum levels of the vitamin are substantially higher when measured by the now widely available radioisotope dilution method than when determined by a more taxing microbiologic assay. More important, the microbiologic assay accurately identified 43 patients who, by other criteria, had well documented pernicious anemia, whereas "serum B12" levels measured by radioisotope dilution . . .
The Psychiatrist's Guide to Diseases of the Nervous System
Authors: Joel E. Dimsdale
Journal: JAMA (1983)

This is a curiously titled book about a complex topic. It is<i>not</i>a review book of basic neurology for board examinations. Instead, it focuses on symptoms that straddle psychiatry and neurology. There are many instances where a patient with symptoms reflecting a neurological illness may see a psychiatrist, or vice versa. Similarly, there are commonly encountered emotional complications to neurological illness and treatment and neurological complications related to psychopharmacological treatment. Unfortunately, this volume is unevenly written. Although some chapters have a remarkable synthetic clarity, many suffer from the author's tendency merely to catalog a host of illnesses without attempting to synthesize an overview. The author begins the book with a long chapter on the neurological examination and various diagnostic tests used in neurology. He attempts to do too much in this one chapter, and the result is a highly telegraphic, hard-to-follow introduction. It would have been better for him
Female doctors are more likely to follow heart failure guidelines than male counterparts
Authors: N. Stafford
Journal: BMJ (2009)

Patients with chronic heart failure who were treated by female doctors received better care than patients cared for by men, a new German study has found. 

It found that male doctors were less likely than women to adhere to guidelines concerning recommended treatments. It also found that men tended to provide better treatment to male patients with heart failure than to female ones.

In the study, published in the European Journal of Heart Failure (http://eurjhf.oxfordjournals.org/cgi/content/full/hfn041, doi:10.1093/eurjhf/hfn041), Magnus Baumhakel, of the department of cardiology at University Hospital of the Saarland in Homburg and …
Steroid Receptors in Breast Cancer
Authors: Eugene R. DeSombre, Paul P. Carbone, Elwood V. Jensen, William L. McGuire, Samuel A. Wells, James L. Wittlife, Mortimer B. Lipsett
Journal: New England Journal of Medicine (1979)

Knowledge of the steroid receptor content of human breast cancer is important for proper diagnosis and for deciding the proper treatment for metastatic disease. Few patients whose breast cancers lack estrogen receptor will benefit from endocrine therapy, while more than half of patients with estrophilin-rich cancers will obtain objective remissions. The probability of objective response to endocrine therapy increases with an increase in the quantity of estrogen receptor in the cancer. Furthermore, patients whose cancers have both estrogen and progestin receptors have a better probability of response than patients whose lesions have only one of the receptors present, although even in such cases the response rate is higher than that seen in patients whose tumors lack both receptors. The data currently available suggest that receptor assays carried out on the primary tumor can be used for prediction of subsequent response to endocrine therapy, even at a later time of recurrent disease. Nonetheless, while sequential assays of receptors in lesions from the same patients are likely to be in agreement, when changes occur they tend to be reductions in amount of receptor or loss of receptor during disease progression . Breast cancer patients with receptor-positive tumors appear to have longer disease-free intervals and prolonged survival when compared with patients whose cancers lack ER, but clearly a part of the prolonged survival relates to response to endocrine therapies. Receptor positivity is frequently associated with well-differentiated tumors, while more poorly differentiated cancers, as well as medullary tumors, in general, and possibly cancers with significant lymphocytic infiltration, are more likely to be receptor negative. While there are some problems reproducing the exact quantitative receptor results among various laboratories assaying the same breast cancer, standard biochemical assays are still the only clinically proven and generally accepted procedure for assessing receptor status of a tumor. Histochemical assays based both on the steroid content of a tumor or using steroid-protein fluorescein complexes, while showing some correlation with standard biochemical assays for estrogen receptor, do not appear to detect receptor protein itself and can not be used instead of standard receptor assays. With the recent availability of monoclonal antibodies to the estrogen receptor, newer assays based on immunochemical procedures are under development and can be expected to provide simpler, less expensive, and more useful biochemical as well as immunohistochemical methods for receptor determination.(ABSTRACT TRUNCATED AT 400 WORDS)
THE EFFECT OF CRYOTHERAPY APPLICATION TO THE ANKLE JOINT ON DYNAMIC POSTURAL STABILITY IN AN ELITE ATHLETIC POPULATION
Authors: K Fullam, B Caulfield, GF Coughlan, E Delahunt
Journal: British Journal of Sports Medicine (2014)

Background Decreased postural stability is a primary risk factor for lower limb musculoskeletal injuries. During athletic competitions, cryotherapy may be applied during short breaks in play or during half-time; however its effects on postural stability remain unclear. Objective To investigate the acute effects of a 15-minute ankle joint cryotherapy application on dynamic postural stability. Design Experimental study. Setting University biomechanics laboratory. Participants 29 elite level collegiate male field-sport athletes. Interventions Participants were tested on the anterior (ANT), posterior-lateral (PL) and posterior-medial (PM) reach directions of the Star Excursion Balance Test (SEBT) both pre- and post- a 15-minute ankle joint cryotherapy application. Main outcome measurements Normalized reach distances, along with sagittal plane kinematics of the hip, knee and ankle joints, as well as associated MVELO and AREAsw of the center-of-pressure (COP) path during the performance of the ANT, PL and PM reach directions of the SEBT. Results There was a statistically significant decrease in ANT, PL and PM reach direction reach distance scores from pre-cryotherapy to post-cryotherapy (P≤.05). No significant differences were observed in hip, knee or ankle joint sagittal plane kinematics (P≥.05). There was a significant decrease in MVELO of the COP path from pre-cryotherapy to post-cryotherapy (P≤.05) in all reach directions (P≤.05). AREAsw of the COP path was significantly decreased from pre-cryotherapy to post-cryotherapy in the ANT and PM reach directions (P≥.05). Conclusions The results of the present study indicate that dynamic postural stability is adversely affected immediately following cryotherapy application to the ankle joint.
Sweeping Passenger Cars While Occupied.
Authors: C. I. Pease
Journal: JAMA (1907)

Linn Grove, Iowa, Oct. 19, 1907. <h3>To the Editor:</h3> —Noticing inThe Journal, Oct. 12, 1907, announcement regarding an order issued by the state commissioner of health of Pennsylvania relating to sleeping cars, I am reminded of a nuisance regularly committed in the day coaches on at least one of the great railway systems leading into Chicago. I allude to the sweeping of the car while occupied, with the result that the car is filled with dust, and invariably a number of passengers are set to coughing. Can not this wrong be righted?
Severe Herpes Simplex Infection
Authors: J Justman, M Zabezhanskaya
Journal: New England Journal of Medicine (1999)

Figure 1. A 30-year-old man with the acquired immunodeficiency syndrome (CD4 cell count, 14 per cubic millimeter) presented with a six-month history of enlarging facial lesions. The lesions had not responded to a six-week course of oral acyclovir (800 mg five times a day). The patient had no history of herpes or any other opportunistic infections. His only other medications were dapsone and fluconazole. On examination, he was afebrile and had extensive, friable, hemorrhagic crusts with impetiginization of the chin and around the nares (Panel A). He also had aphthous ulcers on the soft palate and the anterior portion of . . .
Surgery for ventricular tachycardia associated with right ventricular dysplasia: Disarticulation of right ventricle in 9 of 10 cases
Authors: Kishore Nimkhedkar, Colin J. Hilton, Stephen S. Furniss, John P. Bourke, Brian Glenville, Janet M. McComb, Ronald W.F. Campbell
Journal: Journal of the American College of Cardiology (1992)
Drugs Five Years Later: Trimethoprim-Sulfamethoxazole in the United States
Authors: GARY P. WORMSER
Journal: Annals of Internal Medicine (1979)

After approximately 5 years of clinical use in Great Britain and other European countries, trimethoprim-sulfamethoxazole in fixed-dose combination was introduced into the United States in 1973. As a result of sequential blockade in the biosynthesis of tetrahydrofolic acid, the antimicrobial activity of the combination exceeds that of either agent alone. Although the drug is approved for use in only chronic urinary-tract infection, otitis media, shigellosis, and Pneumocystis carinii pneumonia, many experimental clinical trials suggest that this agent may be useful in a number of other infectious disorders. Trimethoprim-sulfamethoxazole is generally well tolerated even with long-term administration, but its potential for hematologic toxicity and nephrotoxicity must be monitored.