tbuckley/cabot-search huggingface dataset:
Pain after amputation of the lower leg
Authors: A. Low, S. Kapur
Journal: BMJ (2010)

A 59 year old man sustained an open comminuted fracture of the right tibia and fibula in a collision between a car and a motorcycle. This was initially treated by intramedullary nailing and bone grafting of the tibia, with subsequent extensive skin grafting. His mobility remained limited because he developed continuous diffuse pain over the right ankle, which was subsequently fused. The case was complicated by osteomyelitis associated with a dental abscess 21 months later. In view of poor mobility and infection associated with the intramedullary nail, it was agreed to amputate the leg below the knee. He was given bupivacaine epidurally from 24 hours before surgery until three days after surgery, and this provided adequate acute pain control. The stump healed with good cosmetic results and a prosthesis was fitted. The patient, however, still has “a variety of constant pains, including cramp in the foot (related to the length of time using the prosthesis), a burning pain in the right ankle, and the feeling of the lower leg being in a manacle resulting in a hot, intermittent shooting pain, scoring an eight to nine out of 10 pain score.”



### 1 What is the diagnosis?

#### Short answer

Phantom limb pain.

#### Long answer

First recognised by the French military surgeon Ambroise Pare in the 14th century, phantom limb pain is found in 60-85% of patients after amputation of a limb.1 2 3 The pain is usually intermittent; described as sharp, shooting, squeezing, throbbing, or burning in …
Abstract 4614: Karyometry in atypical endometrial hyperplasia: A Gynecologic Oncology Group study
Authors: David S. Alberts, Franciso AR Garcia, Cornelia L. Trimble, James Kauderer, John Curtin, Peter C. Lim, Lisa M. Hess, Steven Silverberg, Richard J. Zaino, Michael Yozwiak, Hubert G. Bartels, Peter Bartels
Journal: Cancer Research (2012)

Abstract Treatment for atypical endometrial hyperplasia (AEH) is based on pathologic diagnosis. About 40% of AEH is found to be carcinoma at surgery. The histopathologic classification of endometrial lesions is a difficult task requiring extensive experience. The Gynecologic Oncology Group (GOG) conducted a study (GOG 167A) that was designed to estimate the frequency of endometrial cancer in hysterectomy specimens in subjects who had a biopsy diagnosis of atypical endometrial hyperplasia. This study's objective is to derive an objective characterization of nuclei from cases diagnosed as AEH or superficially invasive endometrial cancer (SIEC). Cases from GOG study 167A were classified by a central pathology committee as AEH (n=39) or SIEC (n=39). High resolution digitized images of cell nuclei were recorded. Features of the nuclear chromatin pattern were computed. Classification rules were derived by discriminant analysis. Nuclei from cases of AEH and SIEC occupy the same range on a progression curve for endometrial lesions. Cases of AEH and SIEC both comprise nuclei of two phenotypes: hyperplastic characteristics and premalignant/neoplastic characteristics. The principal difference between AEH and SIEC is percentage of premalignant/neoplastic nuclei. When this percentage approaches 50-60% superficial invasion is likely. SIEC may develop already from lesions at the low end of the progression curve. AEH comprises cases which may constitute a low risk group involving &amp;lt;40% of AEH cases. These cases hold a percentage of &amp;lt;20% of nuclei of a preneoplastic phenotype. AEH cases from the central and high end of progression have &amp;gt;40 % of nuclei of the preneoplastic phenotype. Nuclei of the preneoplastic phenotype in AEH lesions are almost indistinguishable from nuclei in SIEC, where this percentage exceeds 60%. While karyometric assessment does not provide a distinctive diagnostic criterion for an individual patient, it does provide a measure of risk for the development of invasive disease. Studies to support the diagnostic assessment of endometrial lesions by computer aided morphometric analyses go back over 30 years. These efforts were aimed at two objectives, the diagnostic distinction between benign and cancer, and procedures that allow a stratification of patients into risk groups for the development of myometrial invasion. The percentage of nuclei of preneoplastic phenotype in AEH lesions might serve as criterion for assessment of risk for the development of invasive disease. 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 4614. doi:1538-7445.AM2012-4614
Autopsy Pathology Procedure and Protocol
Authors: Milton G. Bohrod
Journal: JAMA (1973)

Virchow's little book on autopsy technique, probably the first of its kind, was printed just about a hundred years ago. Since then, most similar books have added little to the subject except some pictures and diagrams. Indeed, Virchow's presentation contains more about the reasons for the methods and is more charmingly written than most of the current books. This book by Weber, Fazzini, and Reagan adds very little to what is in the manuals that have been in use for years. It is not as good as some. Many of the photographs are full of hands and instruments and would be better replaced by diagrams. Whole pages are devoted to reproductions of death certificates and protocol forms. Seventeen pages, at today's inflated publisher's prices, are devoted to reproduction of line drawings of body parts where, at most, one would serve as an example of forms that are easily obtained from
THE MEDICAL RELATIONS OF CERTAIN CONDITIONS OF THE MOUTH.
Authors: L. DUNCAN BULKLEY
Journal: JAMA (1905)

Although not specially occupied with disease of the mouth, 1 have such frequent occasion to inspect the buccal cavity in connection with dermatologic practice, that I have become very much interested in the subject. It also happens that many cases of disease of the tongue, gums, and buccal mucous membrane are sent to me, and many occur in my own practice. The mouth occupies a very prominent place in the economy, as the point of entrance of food, and I need not, in this audience, dwell on the importance of having it, and all within it, in a proper condition. Few, among the laity at least, recognize fully the essential part which is played by the mouth and its appendages in the process of digestion, and consequently in the life and health of the individual. Mastication and proper insalivation are the first steps in digestion, and undoubtedly much ill health
Pharmacological expression in rat hepatocytes of a gene transferred by an adenovirus vector enabled by a chimeric promoter containing multiple cyclic adenosine monophosphate response elements
Authors: Motoyoshi Suzuki, Ravi N. Singh, Ronald G. Crystal
Journal: Hepatology (1998)

Using the adenovirus vector AdCF126(CRE8).Luc to deliver an expression cassette containing multiple cyclic adenosine monophosphate (cAMP) response elements driving the luciferase reporter gene, this study is directed toward evaluating the possibility of controlling genes transferred to the liver using pharmacological agents that raise hepatocyte cAMP levels. Infection of primary rat hepatocytes with AdCF126(CRE8).Luc yielded a low level of luciferase activity that was enhanced 16-fold by the addition of forskolin. Direct intrahepatic administration of the Ad vector in C57Bl/6 mice resulted in low-level luciferase activity that was increased 76-fold by the administration of theophylline and 8-bromo-cAMP to increase cAMP levels. In contrast, animals receiving intrahepatic administration of a control vector containing a constitutively active Rous sarcoma virus (RSV) viral promoter driving the luciferase gene had no response to elevated cAMP. Strikingly, delivery of the vector to the liver by the intravenous route permitted a 258-fold enhancement of liver luciferase activity following administration of the same cAMP-elevating agents. In comparison, a control Ad vector with the RSV promoter was not activated by the elevation in cAMP. The maximum luciferase levels achieved by the combination of AdCF126(CRE8).Luc and pharmacological cAMP elevation was 45-fold greater than that with the RSV promoter. These results show the feasibility of using a chimeric promoter to permit pharmacological induction of high-level expression from an expression cassette transferred to the liver with an adenovirus vector, an approach that may be useful in a variety of liver-related gene-transfer strategies.
Case of Division of the Urethra cured by Operation: Gonorrh a--Urethro-plasty
Authors: M. Ricord
Journal: BMJ (1842)

THE URETHRA.apparatus much impaired, directed his treatment to these points, and with so much success that Mr. T. said for weeks he hald not slept so well, or felt so comfortable, as the first two or three nights after Mlr.
Abstract 1279: Loss of PTEN expression in patients treated with PI3K/AKT/mTOR signaling pathway inhibitors
Authors: Filip Janku, Ignacio Garrido-Laguna, Apostolia M. Tsimberidou, Aung Naing, Siqing Fu, Gerald S. Falchook, Susan C. Abraham, David S. Hong, Razelle Kurzrock
Journal: Cancer Research (2011)

Abstract Background: Loss of PTEN function results in increased PI3K/AKT/mTOR signaling and may predict sensitivity to drugs targeting the PI3K/AKT/mTOR pathway. Methods: Archival tumor samples from patients (N = 202) with diverse cancers referred to the Clinical Center for Targeted Therapy from October 2009 were tested for cytoplasmatic expression of PTEN on immunohistochemistry. Whenever possible, tumor tissue was also analyzed for PIK3CA, RAS (K-, N-), and BRAF mutations using PCR-based DNA sequencing. Consecutive patients with loss of PTEN expression and any tumor type were treated whenever possible with agents targeting the PI3K/AKT/mTOR signaling pathway. Results: Overall, 49 (24%) of 202 patients had loss of PTEN expression. In specific tumor types with a minimum of five patients tested, the loss of PTEN expression was most frequent in squamous cell cervical (60%, 3/5 patients), non-small-cell lung (50%, 4/8), renal (50%, 3/6), uterine (41%, 7/17), gastroesophageal junction/gastric (38%, 3/8), breast cancers (25%, 2/8), melanomas (22%, 6/27), and colorectal cancers (20%, 6/30). Tumors with PTEN loss had frequencies of simultaneous mutations in PIK3CA, RAS (K-, N-), BRAF that were similar to patients with PTEN expression. Of the 49 patients with PTEN loss, 29 (median number of prior therapies, 3) were treated on a protocol that included a PI3K/AKT/mTOR pathway inhibitor. Six of these 29 patients (20.5%) achieved a partial response (PR) (2 uterine cancers, 1 squamous cell cervical cancer; 1 squamous cell head and neck cancer; 1 melanoma; 1 renal cancer) and 8 (27.5%) had stable disease (SD) for &amp;gt;/ = 4 months (total SD&amp;gt;/ = 4 months + PR = 48%). These 29 treated patients had a median progression-free survival of 4.3 months (95% CI, 3.4-5.2). Conclusion: Loss of PTEN expression was found in 24% of patients with various solid tumors. Fourteen of 29 heavily-pretreated patients (48%) had a PR or SD &amp;gt;/ = 4 months, when treated with a PI3K/AKT/mTOR axis inhibitor, suggesting that matching patients with these inhibitors based on PTEN loss merits further exploration. 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 1279. doi:10.1158/1538-7445.AM2011-1279
Follicular lymphoma: 2012 update on diagnosis and management
Authors: Arnold Freedman*
Journal: American Journal of Hematology (2012)

Abstract Disease overview: Follicular lymphoma (FL) is generally an indolent B‐cell lymphoproliferative disorder of transformed follicular center B cells. FL is characterized by diffuse lymphoadenopathy, involvement of bone marrow, splenomegaly, and less commonly other extranodal sites of involvement. In general, cytopenias can occur but constitutional symptoms of fever, nightsweats, and weight loss are uncommon. Diagnosis: Diagnosis is based on histology of preferably a biopsy of a lymph node. Immunohistochemical staining is positive in virtually all cases for cell surface CD19, CD20, CD10, and monoclonal immunoglobulin, as well as cytoplasmic expression of bcl‐2 protein. The overwhelming majority of cases have the characteristic t(14;18) translocation involving the IgH/bcl‐2 genes. Risk stratification: The FL International Prognostic Index prognostic model for FL uses five independent predictors of inferior survival: age &gt; 60 years, hemoglobin &lt; 12 g/dL, serum lactate dehydrogenase &gt; normal, Ann Arbor stage III/IV, number of involved nodal areas &gt; 4. The presence of 0, 1, 2, and ≥ 3 adverse factors defines low, intermediate, and high‐risk disease with median 10‐year survivals in the pre‐rituximab era of ∼71, 51, and 36 months, respectively. With the use of more modern therapies, specifically anti‐CD20 monoclonal antibody, the outcome has improved. Risk‐adapted therapy: Observation continues to be adequate for asymptomatic patients with low bulk disease and no cytopenias. For patients needing therapy, most patients are treated with chemotherapy plus rituximab, which has improved response rates, duration of response, and overall survival. Randomized studies have shown additional benefit for maintenance rituximab both following chemotherapy‐rituximab and single‐agent rituximab. Autologous stem cell transplantation (SCT) has not shown a survival benefit in first remission patients. SCT including both autologous and allogeneic SCT or experimental agent therapy is considered for recurrent disease. Am. J. Hematol. © 2012 Wiley Periodicals, Inc.
Contribution of pulmonary receptors to the heart rate response to acute hypoxemia in rabbits.
Authors: H Kato, A S Menon, F J Chen, A S Slutsky
Journal: Circulation (1988)

We studied the effect of pulmonary afferent activity on the heart rate response to a progressive, isocapnic decrease in oxygen saturation (SaO2) in anesthetized rabbits. To abolish the effect of rapidly adapting receptors, we used inhaled bupivacaine aerosol, and to abolish the effect of slowly adapting stretch receptor activity, we used sulfur dioxide insufflation. The heart rate (HR) response (delta HR/delta SaO2) under control conditions was 0.39 +/- 1.29 beats/min/% (mean +/- SD, n = 11; values greater than 0 indicate a tachycardiac response to hypoxemia). After sulfur dioxide insufflation, all nine rabbits had a bradycardiac response (-2.02 +/- 1.13 beats/min/%), which was significantly less than control (p less than 0.0001). After bupivacaine inhalation, the heart rate response (0.27 +/- 1.04 beats/min/%) was unchanged from control. There were no significant differences in the percent increase of minute ventilation during hypoxemia in all runs. Our results indicate that in rabbits the receptors responsible for the increase in heart rate during progressive hypoxemia are the slowly adapting receptors.
Phospho-p70S6K/p85S6K and cdc2/cdk1 Are Novel Targets for Diffuse Large B-Cell Lymphoma Combination Therapy
Authors: Merry Y. Zhao, Aaron Auerbach, Anisha M. D'Costa, Aaron P. Rapoport, Angelika M. Burger, Edward A. Sausville, Sanford A. Stass, Feng Jiang, Amy M. Sands, Nadine Aguilera, X. Frank Zhao
Journal: Clinical Cancer Research (2009)

This study aimed to identify and evaluate molecular targets for the development of a novel combination chemotherapy to treat refractory and recurrent diffuse large B-cell lymphoma (DLBCL).Lymphoma samples from 38 cases of primary and recurrent DLBCL were analyzed using real-time quantitative PCR of the RPS6KB1 and CDC2 genes, and immunohistochemistry for their gene products p70S6K/p85S6K and cdc2/cdk1. The Farage, Karpas422, Pfeiffer, and Toledo DLBCL cell lines were subsequently treated with rapamycin and UCN-01 alone or in combination. Cell proliferation, apoptosis, and cell cycle progression were analyzed after the drug treatment. In addition, the levels of several key protein kinases involved in the phosphoinositide 3'-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, apoptosis, and cell cycle progression were analyzed in the presence and absence of the drugs.Amplification of the RPS6KB1 and CDC2 genes was found in both primary and recurrent DLBCL. Moreover, the vast majority of these lymphomas (approximately 94%) were strongly positive for phospho-p70S6K and cdc2/cdk1 proteins. The combination of rapamycin and UCN-01 synergistically inhibited the DLBCL cell proliferation by inducing G1 arrest as well as apoptosis by suppressing the phosphorylation of p70S6K/p85S6K and CDC2 expression.RPS6KB1 and CDC2 overexpression is common in DLBCL. Simultaneously targeting the RPS6KB1 and CDC2 products phospho-p70S6K/p85S6K and cdc2/cdk1 is very effective in inhibiting DLBCL proliferation and overcoming drug resistance. This work suggests that multilevel inhibition of the PI3K/Akt/mTOR pathway and double-block of cell cycle progression are effective strategies for DLBCL therapy.
The Apocalyptics: Cancer and the Big Lie
Authors: Jane M. Orient
Journal: JAMA (1985)

Both literal and metaphorical cancers are the subject of this book, which begins as a detective story and ends with an indictment of American science: "When most serious scientists remain silent while... untruths are told to the public for a decade, that is cultural cancer" (p 474). Efron believes that "regulatory science" is an oxymoron and exemplifies Lysenkoism. The investigation begins with Rachel Carson's book<i>Silent Spring</i>and traces what Efron terms the<i>Apocalyptic movement</i>to its present influential position. The Apocalyptics assert that a cancer epidemic will result from the pollution of benign nature by industrial capitalism. The evidence for this supposition is nonexistent, as its proponents admit in material quoted by Efron. Nevertheless, they believe that the establishment of policy is so urgent that there is not even time to determine whether any peril actually exists. Science has become subservient, in her view, to politics, which promises salvation
Rho kinase-1 mediates cardiac fibrosis by regulating fibroblast precursor cell differentiation
Authors: S. B. Haudek, D. Gupta, O. Dewald, R. J. Schwartz, L. Wei, J. Trial, M. L. Entman
Journal: Cardiovascular Research (2009)

AimsHighly proliferative, CD34+/CD45+ fibroblasts derived from monocytic, blood-borne precursor cells play a critical role in the development of fibrosis in a murine ischaemic/reperfusion cardiomyopathy (I/RC) model. The differentiation of human monocytes into fibroblasts in vitro occurs after transendothelial migration (TEM) induced by monocyte chemoattractant protein 1 (MCP-1). Because Rho-associated kinase-1 (ROCK-1) has been implicated in fibrosis and leukocyte TEM, we investigated its involvement in I/RC.
A Guitar Is a Violin Is a Feeling Is an Essay Is Two Letters and One Comment-Reply
Authors: Mark S. Litwin
Journal: JAMA (1986)

In Reply.—  As Gertrude Stein so aptly concluded, A painting is never the thing that it is a painting of; it is a feeling about that thing. And so an essay about a painting of a violin without a violin can still be an essay about a violin. The answer, therefore, to Dr Schwentker's insightful question is yes.
Abstract P6-05-08: Nuclear HER3 localisation plays a role in trastuzumab resistance in HER2-positive breast cancer
Authors: K Hashimoto, I Roxanis, D Generali, D Andreis, C Strina, M Cappelletti, V Macaulay, A Kong
Journal: Cancer Research (2013)

Abstract Background: HER3 is known to locate in the nucleus. Unlike HER4, nuclear HER3 translocation has not been reported to be due to a proteolytic cleavage process by ADAM17 and gamma-secretase. The mechanisms of nuclear HER3 induction and its role in relation to trastuzumab treatment and resistance for HER2-positive breast cancer is unclear. Methods: Using nuclear fractionation and confocal microscopy, nuclear HER3 localisation was investigated in response to trastuzumab with or without ADAM17 inhibitor and gamma-secretase inhibitor in a panel of HER2 expressing cell lines. We also correlated nuclear HER3 expression by immunohistochemistry with treatment response in patients who underwent window trastuzumab study as well as the survival outcome in a cohort of HER2-positive breast cancer patients using Kaplan–Meier survival curves with Log-rank test. Results: HER3 ligand heregulin and trastuzumab was found to induce nuclear HER3 translocation in HER2-positive breast cancer cell lines, including SKBR3. Nuclear HER3 was also enriched in acquired trastuzumab resistant SKBR3 cells (SKBr3-TR). Trastuzumab treatment induced several HER3 fragments and HER3100kD was found to be responsible for nuclear HER3 enrichment by fractionation. This fragment was confirmed to be a specific band of HER3 as shown by HER3 knockdown. Nuclear HER3 was reduced by inhibiting either gamma-secretase or ADAM17 inhibitor. Gamma-secretase or ADAM17 inhibitor reduced HER3100kD in both SKBr3 and SKBr3-TR cells. In HER2-positive breast cancer patients who underwent window trastuzumab study, baseline nuclear HER3 status was not a predictor of response for trastuzumab monotherapy at day 21. However, nuclear HER3 was enriched after trastuzumab treatment in a poor-responder patient. Total HER3 expression level in cytoplasm positively was correlated with poor response to trastuzumab monotherapy in HER2-positive patients (r = 0.67, p = 0.05). There was no statistically significant difference in disease-free survival between positive and negative nuclear HER3 expression but the number of patients was small (n = 87). Further validation to assess nuclear HER3 expression as a prognostic and predictive biomarker in HER2-positive breast cancer patients undergoing trastuzumab treatment will be assessed in randomized tumour samples from FinHER study. Conclusion: Heregulin and trastuzumab treatment seems to induce nuclear HER3 translocation in some of the HER2 positive breast cancer cells. This may be due to proteolytic cleavage of HER3 as it is reduced by ADAM17 or gamma-secretase inhibitor. Enriched nuclear localisation of HER3 seems to be one possible mechanism of acquired resistance to trastuzumab in HER2-positive breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-08.
In vivo reflectance confocal microscopy imaging of melanocytic skin lesions: Consensus terminology glossary and illustrative images
Authors: Alon Scope, Cristiane Benvenuto-Andrade, Anna-Liza C. Agero, Josep Malvehy, Susana Puig, Milind Rajadhyaksha, Klaus J. Busam, Diego E. Marra, Abel Torres, Iva Propperova, Richard G. Langley, Ashfaq A. Marghoob, Giovanni Pellacani, Stefania Seidenari, Allan C. Halpern, Salvador Gonzalez
Journal: Journal of the American Academy of Dermatology (2007)