tbuckley/cabot-search huggingface dataset:
Hoof nail deformity: a previously unknown hereditary nail malformation
Authors: G.W. Jung, T.G. Salopek
Journal: British Journal of Dermatology (2013)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, A 54‐year‐old man who was followed by dermatology regarding a personal history of malignant melanoma was found to have an incidental nail abnormality affecting his bilateral second toenails. The malformed nails had been present since birth, were nonprogressive and were not associated with any symptoms. The patient denied any history of hair, teeth or sweating abnormalities. The patient also had a history of porphyria cutanea tarda, hepatitis C acquired via a blood transfusion, diabetes mellitus type 2 and a 40 pack‐year smoking history. His medications included metformin and sitagliptin. Interestingly, the patient was aware that his nail deformity was a family trait as many of his relatives had a similar alteration dating back to his father, which they kiddingly referred to as the ‘family surname, toe’. He was a child of a nonconsanguineous marriage and had eight siblings, with the patient himself being the sixth eldest (Fig. 1). Over four generations, six members of the family, including the patient himself, appeared to have had the same nail abnormality of varying severity affecting the same digits. Specifically, his father and two of his three daughters were afflicted with malformed bilateral second toenails (Fig. 1). No other family members had a history of melanoma, diabetes or porphyria.
Abstract P2-16-08: Administration of the Novel Antiangiogenic PTC299 in Combination with Aromatase Inhibitors Is Feasible and Shows Antitumor Activity in Metastatic Breast Cancer
Authors: A Tiersten, BP Schneider, M Dickler, M Volm, J Speyer, Y Novik, R Lehman, LA Callahan, CH Darby, LL Miller, H. Miao
Journal: Cancer Research (2010)

Abstract Background: PTC299 is an investigational new drug that suppresses tumor growth by selective post-transcriptional inhibition of tumor VEGF expression. PTC299 demonstrates antitumor activity in both hormone-receptor-positive (HR+) and-negative (HR-) breast cancer xenograft models and eliminates established tumors in aromatase-overexpressing human breast cancer xenografts when given alone or in combination with letrozole. Methods: This study is assessing the feasibility of PTC299 administration in combination with aromatase inhibitors (AIs) in women with HR+ metastatic breast cancer and natural or induced post-menopausal levels of ovarian function. Patients already receiving or newly initiating a standard dose of an AI are coadministered 100 mg BID of oral PTC299 continuously until disease progression. Results: To date, the study has enrolled 24 women with a median [range] age of 57 [26-82] years, ECOG PS of 0 (n=12) or 1 (n=12), to receive PTC299 together with letrozole (n=11), anastrozole (n=6), or exemestane (n=7) for a median [range] duration of ∼16 [3-36] weeks. Combination therapy has been generally well tolerated; AEs have been predominantly Grade 1-2, have usually not been PTC299-related. The most frequent AEs have been headache (25%) and hot flashes (25%). No PTC299 dose reductions or discontinuations due to AEs have occurred. Measures of PTC299 plasma exposure have shown ∼2-fold accumulation, with values reaching steady state by -21 days of treatment; trough values have exceeded those maximally active in xenograft models. Relative to baseline, therapy has been associated with on-study reductions in circulating VEGF concentrations and decreases in tumor perfusion as assessed by DCE-MRI. Antitumor activity includes 3 CRs by PET/CT, 1 PR by PET/CT, and 3 PRs by PET scan. To date, 7/24 (29%) patients have received ≥24 weeks of treatment and 10/24 (42%) patients continue on treatment. Conclusions: Combining PTC299 100 mg BID with standard AI treatment appears feasible. Safety, exposure, pharmacodynamic, and antitumor activity observations have been encouraging. Supported by a grant award from the Department of Defense Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-16-08.
Reciprocal repression between P53 and TCTP
Authors: Robert Amson, Salvatore Pece, Alexandra Lespagnol, Rajesh Vyas, Giovanni Mazzarol, Daniela Tosoni, Ivan Colaluca, Giuseppe Viale, Sylvie Rodrigues-Ferreira, Jessika Wynendaele, Olivier Chaloin, Johan Hoebeke, Jean-Christophe Marine, Pier Paolo Di Fiore, Adam Telerman
Journal: Nature Medicine (2011)
Diffuse Homogeneous Bone Marrow Uptake of FDG in Patients With Acute Lymphoblastic Leukemia
Authors: Kanae Su, Yuji Nakamoto, Koya Nakatani, Kensuke Kurihara, Nobuyuki Hayakawa, Kaori Togashi
Journal: Clinical Nuclear Medicine (2012)

PET (positron emission tomography) using FDG (¹⁸F-fluorodeoxyglucose) has been widely used in the evaluation of various malignancies, but its clinical application to leukemia remains limited. We report a case of leukemia in which diffuse bone marrow uptake of FDG was observed, and bone marrow aspiration subsequently revealed acute lymphoblastic leukemia. It is not easy to differentiate between physiological and pathologic uptake when diffuse homogeneous uptake in bone marrow is observed.
Drug Spotlight Program
Authors: PAUL P. VanARSDEL
Journal: Annals of Internal Medicine (1977)

In the past decade there has been substantial improvement in the quality of drug therapy for asthma. In part, this reflects the greater sophistication and confidence in the use of bronchodilator drugs, after their role in modifying the intracellular concentration of cyclic nucleotides was discovered. Another advance has come from the appearance of adequate information on theophylline blood levels and half-lives and their variability in man. The increasing availability of theophylline blood levels has aided not only in the selection of therapeutic doses but also in determining the effectiveness of newer products that, for example, promise to have a more sustained effect when given by mouth. The plight of asthmatic patients dependent on oral glucosteroid therapy has been substantially eased with the development of new steroid-sparing drugs that are effective by inhalation.
Selenium in coeliac disease.
Authors: B J Collins, P M Bell, D McMaster, A H Love
Journal: BMJ (1984)

Further studies to validate the clinical impression of "accelerated reaction to BCG" in active tuberculosis are needed in order to establish the sensitivity and specificity of the "BCG test."The Nabarro weight for height wall chart is a useful addition to appropriate technology and is currently being tested in several countries.However useful, it is unlikely to be available in every village or squatter settlement in the foreseeable future.The arm band is already widely used and proved to be effective.5
Alterations in cation homeostasis in cultured chick ventricular cells during and after recovery from adenosine triphosphate depletion.
Authors: H Ishida, O Kohmoto, J H Bridge, W H Barry
Journal: Journal of Clinical Investigation (1988)

Alterations in cation homeostasis during and after recovery from myocardial ischemia may account for some of the reversible and irreversible components of myocardial cell injury. To investigate possible mechanisms involved, we exposed cultured layers of spontaneously contracting chick embryo ventricular cells to media containing 1 mM cyanide (CN) and 20 mM 2-deoxyglucose (2-DG), and zero glucose for up to 6 h, and then allowed cultured cells to recover in serum-free culture medium for 24 h. Changes in Na, K, and Ca contents, 42K uptake and efflux, ATP content, cell water content, and lactate dehydrogenase (LDH) release were measured, and compared with changes produced by exposure to 10(-3) M ouabain and severe hypoxia. Exposure to CN and 2-DG caused marked increase in cell Na (sevenfold) and Ca (fivefold) contents, and a decrease in K content (one-fifth normal), coincident with ATP depletion to one-tenth normal levels. This produced only slight cell injury, evidenced by increased LDH release. Recovery for 24 h resulted in return to near normal values (expressed in nanomoles per milligram of protein) of Na, Ca, and ATP contents. However, there was failure of cell K content to return to normal, associated with a persistent reduced net uptake of 42K, and an increase in the rate of 42K efflux. These abnormalities in K homeostasis were associated with a decrease in cell volume and water content per milligram of protein. More marked ATP depletion (to 1/100 normal values) was produced by hypoxia plus 2-DG and zero glucose, and was associated with much more severe cell injury manifested by LDH loss. Ouabain exposure resulted in a much greater Ca gain (20-30-fold), relative to increase in Na content, than did either CN and 2-DG or hypoxia; and ouabain effects were not reversible (after a 15-fold or greater increase in Ca content was produced) and were associated with significant LDH release. We conclude that these cells are resistant to cell injury caused by moderately severe Ca overload and ATP depletion produced by exposure to CN and 2-DG. However, metabolic inhibition of ATP production produces persistent abnormalities in K homeostasis, associated with functional abnormalities.
The Persuasive Appeal of Alternative Medicine
Authors: Ted J. Kaptchuk, David M. Eisenberg
Journal: Annals of Internal Medicine (1998)

Alternative medicine has a major presence and persuasive attraction in the industrialized western world.The extent to which these practices have clinical efficacy according to biomedical criteria is a matter of ongoing research and debate. It may be that independent of any such efficacy, the attraction of alternative medicine is related to the power of its underlying shared beliefs and cultural assumptions. The fundamental premises are an advocacy of nature, vitalism, "science," and spirituality. These themes offer patients a participatory experience of empowerment, authenticity, and enlarged self-identity when illness threatens their sense of intactness and connection to the world. A discussion of these themes may enable conventionally trained clinicians to better understand their patients' attraction to and acceptance of alternative medical therapies.
The Nephrotic Syndrome
Authors: Harry A. Derow
Journal: New England Journal of Medicine (1958)

RECENT advances in knowledge of the nature of the nephrotic syndrome have led to more rational therapy. The purpose of this communication is to review this progress.The nephrotic syndrome is a clinical entity characterized by massive proteinuria, hypoproteinemia, hypoalbuminemia and hyperlipidemia, with or without edema, hematuria, hypertension and azotemia.Students of the disorder are urged to read Leiter's1 scholarly monograph, published in 1931, the critical discussion of the pathogenesis of various manifestations of the nephrotic syndrome presented as a Medical Progress report in this journal in 1948 by Bradley and Tyson,2 Allen's3 recent stimulating paper on the "Clinicopathologic meaning . . .
The Appearance of a Large Mesenteric Varix on a Technetium-99m Red Blood Cell Gastrointestinal Bleeding Study
Authors: JAMES M. MOUNTZ, SHAWN D. RIPLEY, MILTON D. GROSS, BRUCE RICHMOND
Journal: Clinical Nuclear Medicine (1986)

Detection of gastrointestinal bleeding using Tc-99m labeled RBCs has proven to be clinically useful although false-positive images associated with abnormal vascularity remain problematic. The scintigraphic appearance of a large mesenteric varix is presented, and its potential confusion with gastrointestinal bleeding is discussed. Correlative CT and angiographic images are presented.
A specific drug targeting system based on polyhydroxyalkanoate granule binding protein PhaP fused with targeted cell ligands
Authors: Yong-Chao Yao, Xiao-Yong Zhan, Jing Zhang, Xiang-Hui Zou, Zhi-Hui Wang, Yu-Cui Xiong, Jiong Chen, Guo-Qiang Chen
Journal: Biomaterials (2008)
Regulation of PPAR gamma gene expression by nutrition and obesity in rodents.
Authors: A Vidal-Puig, M Jimenez-Liñan, B B Lowell, A Hamann, E Hu, B Spiegelman, J S Flier, D E Moller
Journal: Journal of Clinical Investigation (1996)

The orphan nuclear receptor, peroxisome proliferator-activated receptor (PPAR) gamma, is implicated in mediating expression of fat-specific genes and in activating the program of adipocyte differentiation. The potential for regulation of PPAR gamma gene expression in vivo is unknown. We cloned a partial mouse PPAR gamma cDNA and developed an RNase protection assay that permits simultaneous quantitation of mRNAs for both gamma l and gamma 2 isoforms encoded by the PPAR gamma gene. Probes for detection of adipocyte P2, the obese gene product, leptin, and 18S mRNAs were also employed. Both gamma l and gamma 2 mRNAs were abundantly expressed in adipose tissue. PPAR gamma 1 expression was also detected at lower levels in liver, spleen, and heart; whereas, gamma l and gamma 2 mRNA were expressed at low levels in skeletal muscle. Adipose tissue levels of gamma l and gamma 2 were not altered in two murine models of obesity (gold thioglucose and ob/ob), but were modestly increased in mice with toxigene-induced brown fat ablation uncoupling protein diphtheria toxin A mice. Fasting (12-48 h) was associated with an 80% fall in PPAR gamma 2 and a 50% fall in PPAR gamma mRNA levels in adipose tissue. Western blot analysis demonstrated a marked effect of fasting to reduce PPAR gamma protein levels in adipose tissue. Similar effects of fasting on PPAR gamma mRNAs were noted in all three models of obesity. Insulin-deficient (streptozotocin) diabetes suppressed adipose tissue gamma l and gamma 2 expression by 75% in normal mice with partial restoration during insulin treatment. Levels of adipose tissue PPAR gamma 2 mRNA were increased by 50% in normal mice exposed to a high fat diet. In obese uncoupling protein diphtheria toxin A mice, high fat feeding resulted in de novo induction of PPAR gamma 2 expression in liver. We conclude (a) PPAR gamma 2 mRNA expression is most abundant in adipocytes in normal mice, but lower level expression is seen in skeletal muscle; (b) expression of adipose tissue gamma1 or gamma2 mRNAs is increased in only one of the three models of obesity; (c) PPAR gamma 1 and gamma 2 expression is downregulated by fasting and insulin-deficient diabetes; and (d) exposure of mice to a high fat diet increases adipose tissue expression of PPAR gamma (in normal mice) and induces PPAR gamma 2 mRNA expression in liver (in obese mice). These findings demonstrate in vivo modulation of PPAR gamma mRNA levels over a fourfold range and provide an additional level of regulation for the control of adipocyte development and function.
Validation of the Toronto Alexithymia Scale with Substance Abusers
Authors: Mark G. Haviland, Dale G. Shaw, James P. MacMurray, Michael A. Cummings
Journal: Psychotherapy and Psychosomatics (1988)

The purposes of this paper were to complete factor and item analyses of the Toronto Alexithymia Scale (TAS) in a sample of mixed substance abusers and to examine the correlations between patients' TAS scores and other variables. Results indicate that the TAS is a reliable, valid measure of alexithymia for substance abusers. The factor structure we found is congruent with the theoretical construct and is similar to those published in the normative studies; coefficient alpha reliability was 0.68. Additionally, a high percentage of the subjects (50.4%) scored in the alexithymic range while 24% had scores in the nonalexithymic range. Patients' TAS scores were positively associated with Beck Depression Inventory scores, with a reported paternal history of alcoholism, and with attempted suicide; TAS scores were negatively associated with being Black.
Abstract B50: Selectively targeting prostate cancer with antiandrogen-equipped histone deacetylase inhibitors
Authors: Berkley E. Gryder, Michelle J. Akbashev, Michael K. Rood, Paulette Dillard, Shafiq Khan, Adegboyega K. Oyelere
Journal: Cancer Research (2013)

Abstract Diverse cellular processes relevant to cancer progression are regulated by the acetylation status of proteins, such as chromatin remodeling via histone proteins, controlled by opposing histone deacetylase (HDAC) and histone acetyltransferase (HAT) enzymes. Histone deacetylase inhibitors (HDACi) show great promise in preclinical cancer models, but clinical trials for solid tumors have failed to improve patient survival. This is due in part to an inability of HDACi to effectively accumulate in cancerous cells. To address this problem we designed HDACi with secondary pharmacophores to facilitate selective enrichment in malignant cells. We present the first example of HDACi compounds targeted to prostate tumors by equipping them (via “click” chemistry) with the secondary ability to bind the androgen receptor (AR) with non-steroidal antiandrogen moieties. Leads among these new duel-acting molecules bind to the AR and halt AR transcriptional activity at lower concentrations than clinical antiandrogens. They inhibit key isoforms of HDAC with improved potency over clinically approved HDACi, SAHA. Fluorescent microscopy reveals varying degrees of AR nuclear localization in response to these compounds. These biological properties translate into anticancer activity against hormone independent (AR-) DU145 prostate cancer, and even more so against hormone dependent (AR+) LNCaP, while having greatly reduced toxicity in non-cancerous cells. These compounds illustrate a “smart bomb” approach towards achieving selective, safe, and potent cancer therapies. Citation Format: Berkley E. Gryder, Michelle J. Akbashev, Michael K. Rood, Paulette Dillard, Shafiq Khan, Adegboyega K. Oyelere. Selectively targeting prostate cancer with antiandrogen-equipped histone deacetylase inhibitors. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr B50.
Principles of Neurology
Authors: Donald J. Dalessio
Journal: JAMA (1982)

The second edition of this neurology text follows the first by four years. It maintains its unique organization and is divided into six parts, including sections on neurological diagnosis, manifestations of neurological disease, major categories of neurological disease, disorders of peripheral nerve and muscle, psychiatric conditions, and the neurology of aging. The latter two sections are particularly appealing and distinguish this book from other neurological texts. Furthermore, the organization of the book, in sequence from symptoms to disease, for the most part recapitulates the diagnostic exercise undertaken by physicians, who are approached by patients with complaints rather than diagnostic categories. This book serves to implement and reinforce the diagnostic process; thus, its very structure contributes to learning. Some deficiencies of the first edition, including absence of a discussion of transient global amnesia (no pun intended) and normal pressure hydrocephalus, have been corrected. The importance of computed tomography in neurological diagnosis
OCCUPATIONAL THERAPY WITH "REFRACTORY" PATIENTS
Authors: P. O. O'REILLY, J. R. HANDFORTH
Journal: American Journal of Psychiatry (1955)

The results we have recorded represent no new discoveries. The beneficial effects of suitable occupation in mental illness have been known since the time of Pinel. It is our contention, however, that the staffing and administrative problems of mental hospitals may lead to this form of therapy being available only to the "good" patients and to a neglect of the principle(3) that work per se is not the main thing. We have endeavored to show that, provided it is adapted to the patient's particular needs, occupational therapy can improve the condition of even the most "hopeless" cases. Of the 14 patients who participated in our pilot project, only one has failed to show a striking degree of improvement. The other 13 are still mentally ill, but in relinquishing their positions of isolation, they have become better adapted to the hospital environment. This improvement of interpersonal relationships has been accompanied by reduction of socially illtolerated habits, to such a degree that in 2 cases the relatives wish the patients to return home.
ON THE SURGICAL TREATMENT OF GASTRIC ULCER, ITS COMPLICATIONS AND SEQUELAE: With Sixty Illustrative Cases
Authors: J. Marnoch
Journal: BMJ (1909)

c)ilnexion with it, may be eradicated in accordance with those principles now -generally held -to be necessary in ,dealing with any form of carcinomatous disease.After a study of all the factors, we are in a position to lay down the lines upon which an operation for the removal of a malignant growth beginning in the pyloric region of the stomach should be based.It is essential that the whole growth should be taken away, and such a margin beyond the visible and palpable tumour as shall ensure that the outlying nodules are within the lines of section; that all the lesser curvature, that one-half of the greater curvature, and that an inch at least of the (duodenum should be removed; that all the "primary" glands at least should be taken (these are the lower .andupper coronary, the right paracardial, the suprapyloric, the right suprapancreatic, the right gastro-epiploic upper and lower, :and the retropyloric).The removal of all these parts is possible, and therefore the somewhat mournful view of the possibilities of the surgical treatment of cancer of the stomach taken by several writers are not justified.The difficulties to be encountered will chiefly lie in the removal of the right suprapancreatic glands, but that these difficulties are exaggerated is, 1 think, quite certain.In several cases I have, by using the "gauze stripping" method, removed the glands without any injury either to the hepatic artery or to the pancreas.The following are the steps of the operation, as briefly outlined as possible:1.The free opening of the abdomen in or near the middle line; the inspection of the parts; the packing of swabs around the area to be engaged in the operation, so as to avoid any soiling of the parts.Nothing except the viscera at the moment engaged in the operation should be visible.
Short-Course Antimicrobial Treatment for Acute Otitis Media
Authors: Jack L. Paradise
Journal: JAMA (1997)

IN RECENT years a number of authors—this author among them—have called for restricting, in varying degree, the use of antimicrobials in treating otitis media.<sup>1-5</sup>Two factors have prompted these recommendations: compelling evidence that selective pressure from antimicrobial use contributes importantly to the rising prevalence of infections caused by multidrug resistant<i>Streptococcus pneumoniae</i>,<sup>6,7</sup>and the fact that otitis media accounts for a large proportion of all antimicrobial use. For example, in 1986, of 44.5 million office-based prescriptions for antimicrobials for children younger than 10 years, 42% were for otitis media<sup>8</sup>; while in 1990,1 or more drugs—mainly antimicrobials—were prescribed at more than 80% of the estimated 24.5 million visits to physicians' offices for otitis media.<sup>9,10</sup>Of those visits, children younger than 2 years accounted for 33.3%; children aged 2 to 5 years, 29.2%; and children aged 6 to 14 years, 17.9%.<sup>9</sup>In a recent prospective study, antimicrobial
Lactoferrin acts on Ia-like antigen-positive subpopulations of human monocytes to inhibit production of colony stimulatory activity in vitro.
Authors: H E Broxmeyer
Journal: Journal of Clinical Investigation (1979)

The relationship between Ia-like antigens (Ia-antigens) on human monocytes and the ability of lactoferrin (LF) to inhibit the production of colony stimulatory activity (CSA) for granulocyte and macrophage colony formation was investigated. Complement-dependent cytotoxicity of human monocytes by antiserum to Ia-antigen-reduced CSA production by 50%. LF decreased CSA production by monocytes but had no influence on monocytes insensitive to anti-Ia and complement. Anti-Ia in the absence of complement had no effect on production of CSA but blocked the inhibitory action of LF. This suggsts that LF inhibits production of CSA from an Ia-antigen-positive subpopulation of human blood monocytes. This may be of relevance to the regulation of myelopoiesis.