tbuckley/cabot-search huggingface dataset:
Pretreatment Positron Emission Tomography With [<sup>18</sup>F]Fluorodeoxyglucose for Head and Neck Squamous Cancer
Authors: Vinidh Paleri, Ivan Zammit-Maempel
Journal: Journal of Clinical Oncology (2010)

The authors are to be congratulated on the first multicenter prospective study evaluating the role of fluorodeoxyglucose positron emission tomography (FDG-PET) scans in head and neck cancer.The study methodology rightly compares the stages obtained from the images to the histologic stages.The FDG-PET scans in this study have been shown to have diagnostic efficacy rates comparable with conventional imaging with respect to assessment of the primary sites.Several studies and a European systematic review 2 have shown substantially higher figures for conventional imaging (Ͼ 80% for sensitivity and Ͼ 60% for specificity) using histopathology as the gold standard.We are concerned about the low sensitivity (9%) and specificity (37%) rates demonstrated by conventional imaging (computed tomography and magnetic resonance imaging) in this study for patients in whom there is discordance between conventional imaging and FDG-PET imaging.Although we appreciate that this may be a sub-group within the whole cohort, the reports of this study cannot be placed in context unless the rates of diagnostic efficacy for the patients who had concordance in both imaging modalities are reported.The authors have failed to mention this in the discussion as well.The only conclusion that can be drawn from this article is the high sensitivity of PET-FDG scans.Given the poor diagnostic efficacy of conventional imaging in their cohort, the results regarding change of TNM stage and treatment plan should be interpreted with caution.
Platelet Aggregation as a Sign of Septicemia in Thermal Injury
Authors: Dale H. Cowan, Lynda S. Bowman, Richard B. Fratianne, Farooq Ahmed
Journal: JAMA (1976)

Serial measurements of coagulation activity, platelet counts, and platelet aggregation were done in patients with full-thickness burns involving 25% or more of body surface area to detect specific changes that might correlate with the onset of septicemia. Mean and maximal values for prothrombin time, partial thromboplastin time, thrombin time, activities of factor V and factor VIII, and concentrations of fibrinogen and fibrinogen-related antigens observed in the presence of bacterial septicemia did not differ significantly from those observed in the absence of septicemia. Mean platelet counts were significantly less with sepsis, but values in individual subjects were not indicative of the presence of septicemia. By contrast, platelet aggregation in response to adenosine diphosphate, epinephrine, and collagen always became severely abnormal with the onset of septicemia but not in the absence of sepsis.
Reduction in Asthma Deteriorations in Subjects With Persistent Asthma Uncontrolled on Low-, Medium-, or High-Dose Inhaled Corticosteroids: A Pooled Analysis From Three Clinical Trials Using Combined Mometasone Furoate/Formoterol
Authors: S.F. Weinstein, R.A. Nathan, E.O. Meltzer, D. Gates, H. Nolte
Journal: Journal of Allergy and Clinical Immunology (2011)
Abstract 784: Plasmacytoid urothelial carcinoma: Molecular and histopathological characterization of a rare variant of bladder cancer
Authors: Robert Stoehr, Bastian Keck, Anja Rogler, Ferdinand Hofstaedter, Hans-Martin Fritsche, Jan Lehmann, Rodolfo Montironi, Mathilde Sibony, Bernd Wullich, Arndt Hartmann
Journal: Cancer Research (2010)

Abstract AIM: The plasmaycytoid urothelial carcinoma (PUC) is a rare variant of urothelial carcinoma. To date only few cases have been reported and molecular data are not published yet. Therefore, we analysed clinical, histopathological and molecular features in a series of 32 PUC. METHODS: Expression of CK7, CK20, PAN-CK, p53, Ki67, CD138, E-cadherin and beta-catenin was analysed immunohistochemically on a tissue microarray. UroVysion FISH was performed to asses ploidy status. After microdissection and DNA isolation, FGFR3 and PIK3CA mutation status were determined using SNaPshot analysis. P53 mutation analysis was performed by direct sequencing of exons 5-9. Clinical data available from 16 PUC were compared to 269 patients with conventional locally advanced urothelial bladder cancer within a randomized multicenter trial (AUO-AB 05/95). RESULTS: PUC were usually diagnosed in advanced pathologic stage (64% pT3, 23% pT4) with 60% metastatic disease. Overall survival of PUC treated with cystectomy and adjuvant chemotherapy was lower than of patients with conventional locally advanced bladder cancer (23.3 vs. 49.9 months, p=0.051). 87% of PUCs showed loss or strongly reduced expression of E-cadherin. Beta-catenin was completely absent in 22.5% and associated with loss of E-cadherin (p=0.033). 16.7% of PUC showed a nuclear staining for beta-catenin, which was more frequent in E-cadherin negative PUC. CK20 expression was abnormal in all cases. 22.6% of PUCs were negative for CK7. 97% of PUC displayed a positive PAN-CK staining. 78% coexpressed CD138. Nuclear accumulation of P53 was found in 68.4% of E-cadherin negative PUC, but only in 27.2% of E-cadherin positive ones. p53 mutations were found in 9/31 cases. 69% of PUC showed increased Ki67 labelling index (&amp;gt;15%). FISH displayed PUC as highly aneuploid tumors. Relative deletion of 9p21 was found in 70%. No mutations were found in FGFR3 and PIK3CA. CCONCLUSIONS: PUC showed molecular and histopathologic features of aggressive bladder cancer. Prognosis in locally advanced PUC treated with adjuvant chemotherapy seems to be unfavourable in comparison to conventional bladder cancer. Loss of E-Cadherin is present in the majority of PUC and is associated with a higher degree of p53 and beta-catenin accumulation, which is in line with the high metastatic potential of PUC. CD 138 is not suitable for differential diagnosis to plasmocytoma. PAN CK is an important diagnostic tool for clarification of the epithelial origin of PUC as there are cases negative for CK7 and CK20. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 784.
The Regulatory T Cell–Associated Transcription Factor FoxP3 Is Expressed by Tumor Cells
Authors: Lisa M. Ebert, Bee Shin Tan, Judy Browning, Suzanne Svobodova, Sarah E. Russell, Naomi Kirkpatrick, Craig Gedye, Denis Moss, Sweet Ping Ng, Duncan MacGregor, Ian D. Davis, Jonathan Cebon, Weisan Chen
Journal: Cancer Research (2008)

Abstract FoxP3 is a member of the forkhead family of transcription factors critically involved in the development and function of CD25+ regulatory T cells (Treg). Until recently, FoxP3 expression was thought to be restricted to the T-cell lineage. However, using immunohistochemistry and flow cytometric analysis of human melanoma tissue, we detected FoxP3 expression not only in the tumor infiltrating Treg but also in the melanoma cells themselves. FoxP3 is also widely expressed by established human melanoma cell lines (as determined by flow cytometry, PCR, and Western blot), as well as cell lines derived from other solid tumors. Normal B cells do not express FoxP3; however, expression could be induced after transformation with EBV in vitro and in vivo, suggesting that malignant transformation of healthy cells can induce FoxP3. In addition, a FOXP3 mRNA variant lacking exons 3 and 4 was identified in tumor cell lines but was absent from Treg. Interestingly, this alternative splicing event introduces a translation frame-shift that is predicted to encode a novel protein. Together, our results show that FoxP3, a key regulator of immune suppression, is not only expressed by Treg but also by melanoma cells, EBV-transformed B cells, and a wide variety of tumor cell lines. [Cancer Res 2008;68(8):3001–9]
Lessons in leadership
Authors: Aidan Halligan
Journal: Journal of the Royal Society of Medicine (2012)

‘There is nothing more difficult to carry out, nor more doubtful of success, nor more dangerous to handle, than to initiate a new order of things. For, the reformers have enemies in all those who benefit by the old order and only lukewarm support from those who profit by the new order, because of the incredulity of mankind, who do not truly believe in anything new, until they have the actual experience of it’ Niccolo Machiavelli (1469–1527)
Cell Renewal Patterns
Authors: Joseph Post, Joseph Hoffman
Journal: New England Journal of Medicine (1968)

IF all the many different cell populations of man were renewed continually, the organs they comprise would function normally, and their host would live on forever. Although this state of affairs might produce difficulties of its own, it would solve many biologic problems that occur as a consequence of the failure of renewal of certain cell populations. In this presentation an examination is made of the patterns of cell renewal, in vivo, in several normal and abnormal cell populations as well as in experimentally induced modifications thereof. Some relations of these data to human cancer and aging are considered.The . . .
Grassroots Grappling: Ethics Committees at Rural Hospitals
Authors: Denise A. Niemira
Journal: Annals of Internal Medicine (1988)

Institutional ethics committees are a well-established mechanism for dealing with ethical dilemmas at large health-care institutions. The presence of these committees at small rural hospitals is a recent phenomenon. Because such hospitals are nonspecialized and isolated and have limited resources, they do not naturally encourage the development and growth of ethics committees. The experience of larger institutions with such committees is not readily adaptable, and role models are lacking. The experience of rural Vermont hospitals with ethics committees shows that these committees can function fully at small hospitals and have three stages of development. To accelerate the evolution of ethics committees at small rural hospitals, networking between these hospitals and an association with academic centers are needed. State medical societies can also support these committees by endorsing and sharing resources.
Crry, a complement regulatory protein, modulates renal interstitial disease induced by proteinuria
Authors: Yuichi Hori, Koei Yamada, Norio Hanafusa, Toshihiro Okuda, Noriko Okada, Toshio Miyata, William G. Couser, Kiyoshi Kurokawa, Toshiro Fujita, Masaomi Nangaku
Journal: Kidney International (1999)
Treatment of Progressive Myoclonic Epilepsy with Mephenesin
Authors: R. E. Kelly, D. R. Laurence
Journal: BMJ (1955)

During an investigation of the effect of mephenesin on certain cerebral dysrhythmias it was found that the drug abolished myoclonus in two cases of progressive myo- clonic epilepsy, and it has since proved possible to con- trol thshitherto intractable symptom of the disease by using very heavy dosage of mephenesin.The disease was first clearly described by Unverricht (1891).The patients have occasional attacks of grand mal, but their major disability is myoclonus, in the pro- duction of which there is a strong reflex element (Dawson, 1947).The disease progresses until they exist in " status myoclonicus " and die of exhaustion and inanition within four to five years of the onset.Often there are signs of a cerebellar disturbance (Ramsay-Hunt, 1921), and cere- bellar changes are found at necropsy (Hodskins and Yakovlev, 1929).Early in the course of the disease the myoclonus may respond to the usual anticonvulsants, but it soon becomes resistant to and uncontrollable by drugs without produc- ing incapacitating cerebral depression.Bradshaw (1954) reported that myoclonus may be partially suppressed by phenacemide (" phenurone "), but this is the only drug that has appeared to offer any relief, and the relief afforded was apparently not striking.Case 1 A girl aged 16 was admitted to St. Thomas's Hospital in March, 1952.She had previously been a patient at the National Hospital, Queen Square, under the care of Dr. S. P. Meadows.She had suffered from grand mal for eight years and myoclonus for seven years.She had been helpless for four years, could not feed herself or leave her bed, and her
Association with HSP90 Inhibits Cbl-Mediated Down-regulation of Mutant Epidermal Growth Factor Receptors
Authors: Seungchan Yang, Shimian Qu, Marianela Perez-Tores, Ayana Sawai, Neal Rosen, David B. Solit, Carlos L. Arteaga
Journal: Cancer Research (2006)

Abstract Activating mutations in the epidermal growth factor receptor (EGFR), localized in the activation loop within the kinase domain, have been discovered in non–small cell lung cancers (NSCLC). Most of these mutants are exquisitely sensitive to EGFR tyrosine kinase inhibitors, suggesting that they generate receptor dependence in the cancers that express them. 32D cells stably expressing EGFR-L861Q and EGFR-L858R but not wild-type EGFR exhibited ligand-independent receptor phosphorylation and viability. Ligand-induced receptor down-regulation (LIRD) was impaired in mutant-expressing cells. The EGFR mutants were constitutively associated with the E3 ubiquitin ligase Cbl but did not associate with the adaptor protein CIN85 on the addition of ligand. Inhibition of HSP90 activity with geldanamycin restored Cbl function as indicated by receptor ubiquitination and LIRD. These results suggest that EGFR mutants form defective endocytic complexes. In addition, HSP90 plays a role in maintaining the functional conformation of EGFR mutants and protecting activated receptors from LIRD. (Cancer Res 2006; 66(14): 6990-7)
Plasma and Cerebrospinal Fluid Pharmacokinetics of Imatinib after Administration to Nonhuman Primates
Authors: Kathleen Neville, Robert A. Parise, Patrick Thompson, Alexander Aleksic, Merrill J. Egorin, Frank M. Balis, Leticia McGuffey, Cynthia McCully, Stacey L. Berg, Susan M. Blaney
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Imatinib mesylate (Gleevec, Glivec, STI571, imatinib) is a potent tyrosine kinase inhibitor approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. The role of imatinib in the treatment of malignant gliomas and other solid tumors is being evaluated. We used a nonhuman primate model that is highly predictive of the cerebrospinal fluid penetration of drugs in humans to study the pharmacokinetics of imatinib in plasma and cerebrospinal fluid (CSF) after i.v. and p.o. administration. Experimental Design: Imatinib, 15 mg/kg i.v. over 30 min (n = 3) or 30 mg/kg p.o. (n = 3), was administered to nonhuman primates. Imatinib was measured in serial samples of plasma and CSF using high-pressure liquid chromatography with UV absorbance or mass spectroscopic detection. Pharmacokinetic parameters were estimated using model-independent methods. Results: Peak plasma imatinib concentrations ranged from 6.4 to 9.5 μm after i.v. dosing and 0.8 to 2.8 μm after p.o. dosing. The mean ±SD area under the plasma concentration versus time curve was 2480 ±1340 μm·min and 1191 ±146 μm·min after i.v. and p.o. dosing, respectively. The terminal half-life was 529 ±167 min after i.v. dosing and 266 ±88 min after p.o. dosing. After i.v. dosing the steady state volume of distribution was 5.9 ±2.8 liter/kg, and the total body clearance was 12 ±5 ml/min/kg. The mean peak CSF concentration was 0.25 ±0.07 μm after i.v. dosing and 0.07 ±0.04 μm after p.o. dosing. The mean CSF:plasma area under the plasma concentration versus time curve ratio for all of the animals was 5% ±2%. Conclusions: There is limited penetration of imatinib into the CSF of nonhuman primates after i.v. and p.o. administration.
Court delays takeover of Derbyshire practice
Authors: Owen Dyer
Journal: BMJ (2006)

A contract giving control of a Derbyshire general practice to a US health management company has been put on hold after a legal challenge from a local resident.

UnitedHealth Europe, a subsidiary of the Minnesota based United Health Group, won the bidding process to manage a general practice in the former mining village of Creswell, which includes a branch surgery in the nearby village of Langwith ( BMJ 2006;332: 194, 28 Jan).

But Scarcliffe Parish Council, which administers Langwith, voted unanimously to oppose the award, …
Medicine's core values
Authors: R Smith
Journal: BMJ (1994)

fractures and cancers.For other diseases few agreed case definitions exist8 and when they exist they are rarely used.Tackling this comprehensively would be a massive task and, given the rate with which knowledge is advanc- ing, one that would be doomed to permanent obsolescence.There is, however, a strong case for clinicians to come together, locally or nationally, to develop and disseminate agreed definitions of the most important diagnoses, pro- cedures, and complications so that, when information is produced, everyone speaks the same language.This requires more than the substitution of one set of words, such as those associated with Read codes, for existing classifications.It will sometimes require research to develop validated tools that can be used to determine whether a patient has a particular disorder and, equally importantly, how much of it he or she has.These studies, and others, also support the view that ownership of data contributes to accuracy.9Yet this may not mean that information systems based on separate specialties are always a good thing.In too many hospitals they do not interface with the routine data system and therefore can duplicate work.Also, systematic training for specialty based coders should be available, as it is for routine clinical coders.At present some hospitals manage to obtain much better results than others.It is unclear why, and this merits further study.Clearly, many routine administrative data are still in- adequate to support audit, not to mention contracting.Some purchasers are beginning to impose financial penal- ties for inadequate data, although this may encourage providers to focus on completeness rather than accuracy.'0Increased use of clinical data in contracting may improve some aspects of accuracy, although experience from the United States indicates the potential pitfalls."If comparative audit, based on either routine or ad hoc collection of data, is to succeed, it will require support.The royal colleges and professional associations have done much, but, with the fragmentation of the NHS resulting from increasing competition between providers and the demise of regions, it is far from clear how such activities might be supported in the future.
Prohibiting Genetic Discrimination
Authors: Kathy L. Hudson
Journal: New England Journal of Medicine (2007)

Even before the sequencing of the human genome began in earnest, Americans started worrying about how information about their genetic makeup might be used in harmful ways, and policymakers began considering legislation to prevent misuses of genetic information. The Genetic Information Nondiscrimination Act, which would prohibit health insurers and employers from asking or requiring a person to take a genetic test and from using genetic information in setting insurance rates or making employment decisions, passed unanimously in the Senate in 2003 and again in 2005. The bill remained stalled in the House of Representatives, however, apparently because the House leadership . . .
Adjuvant Chemotherapy for Stage III Colon Cancer: Do Physicians Agree About the Importance of Patient Age and Comorbidity?
Authors: Nancy L. Keating, Mary Beth Landrum, Carrie N. Klabunde, Robert H. Fletcher, Selwyn O. Rogers, William R. Doucette, Diana Tisnado, Steven Clauser, Katherine L. Kahn
Journal: Journal of Clinical Oncology (2008)

We surveyed cancer physicians to understand how patients' age and comorbidity influence adjuvant chemotherapy recommendations and whether physician or practice characteristics also affect these recommendations.National survey of surgeons and medical oncologists caring for patients with colorectal cancer regarding whether they would recommend adjuvant chemotherapy for hypothetical patients with stage III colon cancer who varied by age (55 v 80 years) and comorbid illness (none, moderate, severe congestive heart failure [CHF]). Repeated measures logistic regression was used to assess the influence of patient, physician, and practice characteristics on chemotherapy recommendations.Of 1,096 physicians, nearly all recommended chemotherapy for patients who were 55 years old with no comorbidity (99.0%), 55-years old with moderate CHF (88.6%), or 80 years old with no comorbidity (92.6%); many fewer recommended chemotherapy for 55-year-old patients with severe CHF (24.9%) or 80-year-old patients with moderate (47.2%) or severe (9.0%) CHF (P < .001). Younger physicians (P < .001) were more likely than others to recommend adjuvant chemotherapy overall, although physician factors explained little of the variability in recommendations.Physicians agree with guidelines recommending adjuvant chemotherapy for young, healthy patients with stage III colon cancer but differ widely on recommendations for patients who are older and sicker. Few physician or practice characteristics were associated with recommendations. For older and sicker patients, the individual physicians seen may have a substantial impact on the likelihood of receiving chemotherapy. Understanding better the sources of variation not explained by patients' clinical characteristics may allow improved tailoring of therapy to patients most likely to benefit.
A Study of Family Medicine in Upstate New York
Authors: Gregory J. Riley
Journal: JAMA (1969)

Despite the growing concern over the future of the American family doctor, there have been few studies of his background or current work. In this study 103 randomly selected family physicians in New York state were visited. The data show that these physicians do provide continuing care to family units, a central concept of family medicine. Their satisfaction with their work is apparent, and the use of their services by the public can be judged by their long hours and heavy work loads. These data should provide useful information for those interested in developing realistic training programs for the family doctor of tomorrow.
Assisted Ventilation in Cystic Fibrosis
Authors: John D. Lloyd-Still
Journal: JAMA (1978)

To the Editor.—  I was interested in the article Assisted Ventilation for Patients With Cystic Fibrosis (239:1851, 1978). My colleagues and I 1 have published data previously that support the authors' conclusions. We reviewed the diagnosis, management, and prognosis in 17 cases of infants with cystic fibrosis and severe respiratory distress who were admitted to the Children's Hospital Medical Center, Boston, between 1968 and 1972. There was a 60% mortality overall. Six of the 17 infants were treated with assisted ventilation, of whom only one survived. These figures are almost identical to those of the nine infants (from several cystic fibrosis centers) reviewed by Davis and di Sant'Agnese. Our subsequent experience with assisted ventilation has shown no improvement in the survival of these infants.
Accumulation of ln-111 Tagged White Blood Cells in Heterotopic New Bone
Authors: STEFAN D. MIRON, ANTHONY J. MINOTTI, JEFFREY R. CRASS
Journal: Clinical Nuclear Medicine (1992)

In-111 tagged white blood cells are known to accumulate in various noninfectious conditions of the skeleton, such as healing fractures, at sites of bone marrow aspiration, or at bone graft donor sites. A case is presented with leukocyte accumulation at the sites of heterotopic new bone formation.