tbuckley/cabot-search huggingface dataset:
Pharmacokinetic-Pharmacodynamic Relationships for the Heat Shock Protein 90 Molecular Chaperone Inhibitor 17-Allylamino, 17-Demethoxygeldanamycin in Human Ovarian Cancer Xenograft Models
Authors: Udai Banerji, Michael Walton, Florence Raynaud, Rachel Grimshaw, Lloyd Kelland, Melani Valenti, Ian Judson, Paul Workman
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To establish the pharmacokinetic and pharmacodynamic profile of the heat shock protein 90 (HSP90) inhibitor 17-allylamino, 17-demethoxygeldanamycin (17-AAG) in ovarian cancer xenograft models. Experimental Design: The effects of 17-AAG on growth inhibition and the expression of pharmacodynamic biomarkers c-RAF-1, CDK4, and HSP70 were studied in human ovarian cancer cell lines A2780 and CH1. Corresponding experiments were conducted with established tumor xenografts. The variability and specificity of pharmacodynamic markers in human peripheral blood lymphocytes (PBL) were studied. Results: The IC50 values of 17-AAG in A2780 and CH1 cells were 18.3 nmol/L (SD, 2.3) and 410.1 nmol/L (SD, 9.4), respectively. Pharmacodynamic changes indicative of HSP90 inhibition were demonstrable at greater than or equal the IC50 concentration in both cell lines. Xenograft experiments confirmed tumor growth inhibition in vivo. Peak concentrations of 17-AAG achieved in A2780 and CH1 tumors were 15.6 and 16.5 μmol/L, respectively, and there was no significant difference between day 1 and 11 pharmacokinetic profiles. Reversible changes in pharmacodynamic biomarkers were shown in tumor and murine PBLs in both xenograft models. Expression of pharmacodynamic markers varied between human PBLs from different human volunteers but not within the same individual. Pharmacodynamic biomarker changes consistent with HSP90 inhibition were shown in human PBLs exposed ex vivo to 17-AAG but not to selected cytotoxic drugs. Conclusion: Pharmacokinetic-pharmacodynamic relationships were established for 17-AAG. This information formed the basis of a pharmacokinetic-pharmacodynamic-driven phase I trial.
INTERMITTENT TICK FEVER.PRELIMINARY REPORT ON A NEW TYPE OF FEVER DUE TO TICK BITE (IXODIASIS).
Authors: CHARLES F. KIEFFER
Journal: JAMA (1907)

The older physicians in the Rocky Mountain regions have always insisted that there is a special type of fever indigenous to this section of the country. This fever or, as it appears to me, groups of fevers, has been given various names, but principally that of mountain fever. The group has simply been dismissed in recent years, although many good observers still hold that there is a type of fever which is neither malaria nor typhoid. It has been very generally held that exact laboratory methods would place these supposed specific fevers as aberrant types of one or the other of the two diseases. A beginning has been made, however, in the description of the "Spotted Fever of the Rocky Mountains." This affection is now generally conceded a specific nature. So far as known it is very closely limited to narrow tracts of country and has a dreadful mortality rate.
T(8;21) With a phenotype of chronic myeloid leukemia
Authors: Wendy H. Raskind, Thalia Papayannopoulou, William P. Hammond
Journal: American Journal of Hematology (1988)

Abstract A myeloproliferative disorder having the phenotype of chronic myeloid leukemia (CML) with t(8;21) is reported. Neither t(9;22) nor a DNA rearrangement in the bcr region was detected. The presence of t(8;21), in contrast with previous experience, does not appear to prevent full maturation of the granulocytic series.
Interaction Between Vitamin A and Plastic Intravenous Fluid Bags
Authors: Win L. Chiou
Journal: JAMA (1973)

<h3>To the Editor.—</h3> Since the introduction of the flexible plastic intravenous fluid bags (Viaflex, marketed by Travenol Laboratories, Inc., Morton Grove, Ill) in 1971, their use in this country has received wide acceptance. There are some advantages of these bags over the traditional glass counterparts such as being lighter in weight, easier to store, and relatively unbreakable. However, their potential clinical problems such as sorption of drugs and leaching of chemicals from the bags do not appear to have been critically evaluated and reported in the literature. In our preliminary study on the sorption of some commonly used vitamins onto the bags, we were surprised to find that vitamin A (in the form of retinol acetate), at concentrations within the clinically used range, was strongly sorbed onto the bags. For example, 78% of 200 ml aqueous solution (with an initial concentration of 3μg per ml solubilized in 0.01% polysorbate 80)
Functional and electrophysiological consequences of chronic treatment with spironolactone in comparison with lisinopril during low-flow ischemia and reperfusion in isolated rat hearts
Authors: A. Rochetaing, A. Furber, L. Marescau, C. Barbo, P. Geslin, A. Tadéi, P. Kreher
Journal: Journal of the American College of Cardiology (1998)
THE ETIOLOGY OF LEPROSY.—A CRITICISM OF SOME CURRENT VIEWS.
Authors: P. S. ABRAHAM
Journal: JAMA (1889)

Putting to one side, for the present, the bacillus, which all pathologists agree is to be found in every leprous neoplasm, the supposed etiological factors of leprosy which have been most considered of late years, are three, viz., (I.) Heredity. (2.) A diet of fish. (3.) Contagion. <i>The theory of heredity</i>has had immense support, both lay and professional, and it is curious to observe how loth some medical authors are to set themselves free from its trammels, or to question its influence in propagating the disease, even though many of the facts which they themselves adduce seem obviously to lead to quite another conclusion. As Mr. Jonathan Hutchinson points out,<sup>1</sup>the fact of leprosy occasionally appearing in healthy immigrants, and just as severely as if such persons belonged to leper families, is enough to prove that hereditariness goes for little or nothing in its causation. It is indeed
Dose Response to Vitamin D Supplementation in Postmenopausal Women
Authors: J. Christopher Gallagher, Adarsh Sai, Thomas Templin, Lynette Smith
Journal: Annals of Internal Medicine (2012)

This article has been corrected. The original version (PDF) is appended to this article as a supplement. Background: Serum 25-hydroxyvitamin D (25-[OH]D) is considered the best biomarker of clinical vitamin D status. Objective: To determine the effect of increasing oral doses of vitamin D3 on serum 25-(OH)D and serum parathyroid hormone (PTH) levels in postmenopausal white women with vitamin D insufficiency (defined as a 25-[OH]D level ≤50 nmol/L) in the presence of adequate calcium intake. These results can be used as a guide to estimate the Recommended Dietary Allowance (RDA) (defined as meeting the needs of 97.5% of the population) for vitamin D3. Design: Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00472823) Setting: Creighton University Medical Center, Omaha, Nebraska. Participants: 163 healthy postmenopausal white women with vitamin D insufficiency enrolled in the winter or spring of 2007 to 2008 and followed for 1 year. Intervention: Participants were randomly assigned to receive placebo or vitamin D3, 400, 800, 1600, 2400, 3200, 4000, or 4800 IU once daily. Daily calcium supplements were provided to increase the total daily calcium intake to 1200 to 1400 mg. Measurements: The primary outcomes were 25-(OH)D and PTH levels at 6 and 12 months. Results: The mean baseline 25-(OH)D level was 39 nmol/L. The dose response was curvilinear and tended to plateau at approximately 112 nmol/L in patients receiving more than 3200 IU/d of vitamin D3. The RDA of vitamin D3 to achieve a 25-(OH)D level greater than 50 nmol/L was 800 IU/d. A mixed-effects model predicted that 600 IU of vitamin D3 daily could also meet this goal. Compared with participants with a normal body mass index (<25 kg/m2), obese women (≥30 kg/m2) had a 25-(OH)D level that was 17.8 nmol/L lower. Parathyroid hormone levels at 12 months decreased with an increasing dose of vitamin D3 (P = 0.012). Depending on the criteria used, hypercalcemia occurred in 2.8% to 9.0% and hypercalciuria in 12.0% to 33.0% of participants; events were unrelated to dose. Limitation: Findings may not be generalizable to other age groups or persons with substantial comorbid conditions. Conclusion: A vitamin D3 dosage of 800 IU/d increased serum 25-(OH)D levels to greater than 50 nmol/L in 97.5% of women; however, a model predicted the same response with a vitamin D3 dosage of 600 IU/d. These results can be used as a guide for the RDA of vitamin D3, but prospective trials are needed to confirm the clinical significance of these results. Primary Funding Source: National Institute on Aging.
Focus: Sydney Confusion over radiation risk from phone towers
Authors: S. Chapman
Journal: BMJ (1997)

After growing protests from residents about the alleged dangers from radio frequency radiation from mobile phone towers, several local councils in Sydney have issued regulations on the distances away from buildings that towers can be located.

Note it is “distances” not “distance.” For example, according to the rules of one council, no tower can be placed within 300 m of your house. But the towers can come as close to your workplace as specified in any deal struck between your employer and a phone company. They can plonk one right outside your office or factory window.

The council stated that it had considered the “potential health impact.” Presumably it believes that workers are more …
F-18 FDG and C-11 Methionine PET/CT in Intracranial Dural Metastases
Authors: Maria Mathew D'Souza, Abhinav Jaimini, Madhavi Tripathi, Naresh Garg, Rajnish Sharma, Anupam Monndal, Rajendra P. Tripathi
Journal: Clinical Nuclear Medicine (2012)

A 58-year-old woman with breast carcinoma, after mastectomy, radiotherapy, and chemotherapy, underwent a whole-body F-18 FDG PET/CT for restaging, which revealed multiple skeletal metastasis. Hypometabolism was noted in the right frontal lobe. The patient subsequently underwent a C-11 methionine brain scan, which demonstrated multiple dural-based metastatic foci confirmed on contrast-enhanced MR. FDG PET has limitations in brain tumor detection. Amino acid tracers are particularly attractive for imaging of brain tumors because of relatively high tumor to brain activity ratios.
Adenovirus–Retrovirus Hybrid Vectors Achieve Highly Enhanced Tumor Transduction and Antitumor Efficacy In Vivo
Authors: Shuji Kubo, Kazunori Haga, Atsuko Tamamoto, Donna J Palmer, Philip Ng, Haruki Okamura, Noriyuki Kasahara
Journal: Molecular Therapy (2010)

Murine leukemia virus (MLV)-based replication-competent retrovirus (RCR) vectors have been shown to mediate efficient, selective, and persistent tumor transduction, thereby achieving significant therapeutic benefit in a wide variety of cancer models. To further augment the efficiency of this strategy, we have developed a delivery method employing a gutted adenovirus encoding an RCR vector (AdRCR); thus, tumor cells transduced with the adenoviral vector transiently become RCR vector producer cells in situ. As expected, high-titer AdRCR achieved significantly higher initial transduction levels in human cancer cells both in vitro and in vivo, as compared to the original RCR vector itself. Notably, even at equivalent initial transduction levels, more secondary RCR progeny were produced from AdRCR-transduced cells as compared to RCR-transduced cells, resulting in further acceleration of subsequent RCR replication kinetics. In pre-established tumor models in vivo, prodrug activator gene therapy with high-titer AdRCR could achieve enhanced efficacy compared to RCR alone, in a dose-dependent manner. Thus, AdRCR hybrid vectors offer the advantages of high production titers characteristic of adenovirus and secondary production of RCR in situ, which not only accelerates subsequent vector spread and progressive tumor transduction, but can also significantly enhance the therapeutic efficacy of RCR-mediated prodrug activator gene therapy.
CHANGING CONDITIONS IN VIENNA
Authors: Chester M. Echols
Journal: JAMA (1922)

<h3>To the Editor:</h3> —Perhaps American physicians are interested in knowing how the war and subsequent events have affected Vienna as a teaching center. One hears conflicting reports in America about the medical teaching situation here. The purpose of this letter is to comment not only on present conditions in Vienna, but also on tendencies which point unmistakably to what the future is likely to bring. Today, Vienna still holds first place in Europe as a graduate medical teaching center. Its organization, personnel and prestige have thus far kept the machine going fairly well from sheer force of its own momentum. But even the casual observer must conclude that its days of leadership are numbered. It cannot escape the distintegrating influences of poverty. The amount and variety of clinical material in some departments, indeed in most departments, have lately suffered a severe slump. I learned today that one clinic, which formerly
Pitfalls of Chemotherapy and Antibiotics in Surgery
Authors: Allen G. Rice
Journal: New England Journal of Medicine (1949)

ACCORDING to Webster's dictionary, a pitfall is defined as an error into which the unwary may unsuspectingly drop. By the same authority an error may be one of omission or commission. It may be stated that the pitfalls of chemotherapy and antibiotics are of two kinds: those that are liable to waylay all these agents, and those that are selective in their iniquity. Perhaps the worst error made with these remedies is to endow them as panaceas. True, they cure a few diseases all the time and others some of the time, but never all diseases all the time. The . . .
Serum Enzyme Values in Infectious Mononucleosis
Authors: Melvin B. Black
Journal: JAMA (1969)

<h3>To the Editor:—</h3> The dissociation of serum bilirubin concentration and alkaline phosphatase activity described by Shuster and Ognibene (<b>209</b>:267, 1969) has also been noted in this laboratory. Additional information has been obtained with serum transaminase values and lactic dehydrogenase (LDH) levels with isoenzymes. In acute infectious mononucleosis without icterus, the LDH level is consistently elevated (700 to 1400 units) and the alkaline phosphatase activity may rise to 10 Bodansky units. Despite significant hyperbilirubinemia in infectious mononucleosis, the transaminase values are both consistently below 200 units, the alkaline phosphatase activity below 20 units, and the lethal dose (LD<sub>5</sub>) liver fraction is less than 20%. In infectious hepatitis, the LD<sub>5</sub>is more than 50% in almost all cases and the transaminase values numerically approximate the LDH values.
Evaluation of Retinal Nerve Fiber Layer Progression in Glaucoma
Authors: Christopher Kai Shun Leung, Shu Liu, Robert N. Weinreb, Gilda Lai, Cong Ye, Carol Yim Lui Cheung, Chi Pui Pang, Kwok Kay Tse, Dennis Shun Chiu Lam
Journal: Ophthalmology (2011)
Q fever: epidemiology, clinical features and prognosis. A study from 1983 to 1999 in the South of Spain
Authors: Arı́stides de Alarcón, Jose Luis Villanueva, Pompeyo Viciana, Luis López-Cortés, Rafael Torronteras, Máximo Bernabeu, Elisa Cordero, Jerónimo Pachón
Journal: Journal of Infection (2003)
Nuclear Factor of Activated T3 Is a Negative Regulator of Ras-JNK1/2-AP-1–Induced Cell Transformation
Authors: Ke Yao, Yong-Yeon Cho, H. Robert Bergen, Benjamin J. Madden, Bu Young Choi, Wei-Ya Ma, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2007)

Abstract The c-jun-NH2-kinases (JNK) play a critical role in tumor promoter–induced cell transformation and apoptosis. Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser213 and Ser217, which are located in the conserved SP motif. The transactivation domain of NFAT3 is found between amino acids (aa) 113 and 260 and includes the phosphorylation targets of JNK1 and JNK2. NFAT3 transactivation activity was suppressed in JNK1−/− or JNK2−/− mouse embryonic fibroblast (MEF) cells compared with wild-type MEF cells. Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose-dependent manner by JNK1 or JNK2. Double mutations at Ser213 and Ser217 suppressed NFAT3 transactivation activity; and SP600125, a JNK inhibitor, suppressed NFAT3-induced 3xNFAT-luciferase activity. Knockdown of JNK1 or JNK2 suppressed foci formation in NIH3T3 cells. Importantly, ectopic expression of NFAT3 inhibited AP-1 activity and suppressed foci formation. Furthermore, knockdown of NFAT3 enhanced Ras-JNK1 or JNK2-induced foci formation in NIH3T3 cells. Taken together, these results provided direct evidence for the anti-oncogenic potential of the NFAT3 transcription factor. [Cancer Res 2007;67(18):8725–35]
Creating the patient centered medical home
Authors: B. Roehr
Journal: BMJ (2014)

“Our healthcare system is broken,” says Mark Frazer, a primary care physician in a small private practice in Middletown, a city of about 50 000 in southwestern Ohio. He has embraced the patient centered medical home (PCMH) as a model that is “improving healthcare delivery, patient health, and potentially has the ability to lower costs.”

The transition hasn’t been easy for Frazer, who is now in his second year participating in a demonstration project. He shared that experience and his thoughts on the medical home concept with Capitol Hill staffers at a briefing on 30 May, which was organized by the nonpartisan Alliance for Health Reform.1

The PCMH, coupled with a move away from fee for service reimbursement, are cornerstones of healthcare reform in the US.

Kaiser Permanente, the Geisinger Health System, and other integrated healthcare systems have embodied this approach for decades. They score well in terms of patient health outcomes and satisfaction, while their costs are at or below those of other providers in the same market.

But much of healthcare remains fragmented. Those stakeholders have been scurrying to integrate delivery of care in anticipation of changes in reimbursement by government and private health insurers.

The chief method has been through acquisition. Consolidation among hospitals has been under way for some time and in the past few years that wave has expanded to include purchase of medical specialty and primary care practices. Voluntary coordination of care between independent providers and hospitals has been attempted less frequently.

The principles of a PCMH are clear: “delivering team-based care in a coordinated way that is connected with the community,” is how Amy Gibson, who leads the Patient-Centered Primary Care Collaborative (www.pcpcc.org), describes it. That can take a variety of forms, as can the journey from the current fragmentation to a more …
Safety of Lap-Belt Restraint for Pregnant Victims of Automobile Collisions
Authors: Warren M. Crosby, J. Paul Costiloe
Journal: New England Journal of Medicine (1971)

Of 208 pregnant victims of severe automobile accidents, 28 wore lap belts, and 180 were unrestrained. Lap-belt restraint was associated with a reduction in maternal death from 7.8 to 3.6 per cent, and with an increase in fetal loss from 14.4 to 16.7 per cent. These differences are not statistically significant, and no evidence was obtained that lap-belt restraints increased mortality of either mother or fetus involved in severe accidents. Among unbelted pregnant women involved in severe collisions, the death rate was 33 per cent of those ejected from the car and 5 per cent of those not ejected. The fetal death rate was 47 per cent when the mother was ejected and 11 per cent when she was not. These differences are statistically significant. Thus, lap belts, which usually prevent ejection, may be recommended for pregnant travelers.
P2-220: Radiation pneumonitis (RP) in lung cancer patients treated with chemotherapy (CT) and thoracic radiation (TR): Retrospective analyses of patients treated at a comprehensive cancer center
Authors: Prakash Vishnu, Sridhar Srinivasan, Robert Isaak, Andrew Turrisi, Lance Heilbrun, Raghu Venkataramanamoorthy, Antionette Wozniak, Ayman Soubani, Shirish Gadgeel
Journal: Journal of Thoracic Oncology (2007)
Date of Delivery in Multifetal Pregnancies-Reply
Authors: Hisanori Minakami
Journal: JAMA (1996)

In Reply.  —We agree with Dr Luke that our proposal has limited applicability in the United States. The mean duration of pregnancies may be influenced by racial factors. 1 Maternal height is positively correlated with duration of pregnancy, 2 and maternal body mass index may also be positively correlated with gestational length. 3 Japanese women are shorter and slimmer compared with white American women. Thus, the mean duration of pregnancy among white American women may be longer than that among Japanese women. However, as pointed out by Luke, pregnancy with twins is different from that involving triplets or higher-order pregnancy. Twin pregnancy is apparently different biologically from singleton pregnancy, regardless of race, with respect to the duration of pregnancy, as suggested by our study. The problem is that the definition of term delivery, which may have been derived from populations in which singleton pregnancies accounted for more than 95% of all pregnancies,
Dextran Therapy of Purpura Fulminans
Authors: Joseph H. Patterson, Robert B. Pierce, J. Richard Amerson, W. Lorraine Watkins
Journal: New England Journal of Medicine (1965)

PURPURA fulminans was first described by Guellot1 in 1884. In 1961 Charkes2 reviewed 100 cases; 8 were in children; 3 of them died, and 2 others required amputation. Subsequent case reports reinforce the seriousness of the prognosis.3 , 4 Treatments, with varying degrees of success, have included corticosteroids,3 heparin and warfarin anticoagulation5 and hyperbaric oxygenation.6 Characteristically, ecchymotic areas appear abruptly, usually on the extremities or areas of pressure. Gangrene and hemorrhage follow, with fever, chills, malaise and, occasionally, coma. Various abnormalities of coagulation have been demonstrated, including diminished platelets, insufficient factor V, fibrinogen and prothrombin7 8 9 10 and elevated antithrombin III.9 The etiology is . . .
Durable engraftment of AMD3100-mobilized autologous and allogeneic peripheral-blood mononuclear cells in a canine transplantation model
Authors: Lauri Burroughs, Marco Mielcarek, Marie-Térèse Little, Gary Bridger, Ron MacFarland, Simon Fricker, Jean Labrecque, Brenda M. Sandmaier, Rainer Storb
Journal: Blood (2005)
HOXA9 promotes ovarian cancer growth by stimulating cancer-associated fibroblasts
Authors: Song Yi Ko, Nicolas Barengo, Andras Ladanyi, Ju-Seog Lee, Frank Marini, Ernst Lengyel, Honami Naora
Journal: Journal of Clinical Investigation (2012)

Epithelial ovarian cancers (EOCs) often exhibit morphologic features of embryonic Müllerian duct-derived tissue lineages and colonize peritoneal surfaces that overlie connective and adipose tissues. However, the mechanisms that enable EOC cells to readily adapt to the peritoneal environment are poorly understood. In this study, we show that expression of HOXA9, a Müllerian-patterning gene, is strongly associated with poor outcomes in patients with EOC and in mouse xenograft models of EOC. Whereas HOXA9 promoted EOC growth in vivo, HOXA9 did not stimulate autonomous tumor cell growth in vitro. On the other hand, expression of HOXA9 in EOC cells induced normal peritoneal fibroblasts to express markers of cancer-associated fibroblasts (CAFs) and to stimulate growth of EOC and endothelial cells. Similarly, expression of HOXA9 in EOC cells induced normal adipose- and bone marrow-derived mesenchymal stem cells (MSCs) to acquire features of CAFs. These effects of HOXA9 were due in substantial part to its transcriptional activation of the gene encoding TGF-β2 that acted in a paracrine manner on peritoneal fibroblasts and MSCs to induce CXCL12, IL-6, and VEGF-A expression. These results indicate that HOXA9 expression in EOC cells promotes a microenvironment that is permissive for tumor growth.