tbuckley/cabot-search huggingface dataset:
Changing Gloves Between Vaginal and Rectal Examination: Reinstitution of Old Practices for New Diseases
Authors: George D. Wilbanks
Journal: JAMA (1986)

<h3>To the Editor.—</h3> Old habits tend to stick! As a resident, I was taught by my mentor, the late Professor Bayard Carter of Duke University, to change gloves between the vaginal and rectovaginal examination. This was because of his experience with rectal involvement from lymphogranuloma venereum, which caused rectal stricture. Such strictures were seen in many indigent clinics throughout the South prior to the antibiotic era. I continued this practice probably mainly out of habit but also because it gives one the chance to examine the left side of the pelvis with the left hand; ie, the pads of the fingers naturally face and can palpate the left side of the pelvis while doing the vaginal examination. In doing the rectovaginal examination, the new glove is placed on the right hand, which allows the pads of the fingers to be facing the right side of the pelvis and makes palpation
And Nor Are We
Authors: Claus A. Pierach
Journal: JAMA (1992)

<h3>To the Editor.</h3> —The article by Brancati<sup>1</sup>is objectionable mockery. Furthermore, his ridicule is ill directed: to test for excessive amounts of porphobilinogen can lead to life-saving therapy—it is much more than a "fancy test." Porphyric attacks can be frighteningly real, happen to real people, and have to be searched for—a typical teaching point for morning report. I suggest Dr Brancati look elsewhere for an outlet (sink?) for his forced humor.
Demonstration of a Parathyroid Adenoma with Tc???99m MDP Bone Scintigraphy
Authors: S LAFONTAINE, B LEFEBVRE, R TAILLEFER, J L??VEILL??, C PISON
Journal: Clinical Nuclear Medicine (1984)

LAFONTAINE, S M.D.; LEFEBVRE, B M.D.; TAILLEFER, R M.D.; LÉVEILLÉ, J M.D.; PISON, C M.D., D.Sc Author Information
Phospholipase C-dependent control of cardiac calcium homeostasis involves a TRPC3-NCX1 signaling complex
Authors: P EDER, D PROBST, C ROSKER, M POTESER, H WOLINSKI, S KOHLWEIN, C ROMANIN, K GROSCHNER
Journal: Cardiovascular Research (2006)

Members of the classical transient receptor potential protein (TRPC) family are considered as key components of phospholipase C (PLC)-dependent Ca2+ signaling. Previous results obtained in the HEK 293 expression system suggested a physical and functional coupling of TRPC3 to the cardiac-type Na+/Ca2+ exchanger, NCX1 (sodium calcium exchanger 1). This study was designed to test for expression of TRPC3 (transient receptor potential channel 3) and for the existence of a native TRPC3/NCX1 signaling complex in rat cardiac myocytes.Protein expression and cellular distribution were determined by Western blot and immunocytochemistry. Protein-protein interactions were investigated by reciprocal co-immunoprecipitation and glutathione S-transferase (GST)-pulldown experiments. Recruitment of protein complexes into the plasma membrane was assayed by surface biotinylation. The functional role of TRPC3 was investigated by fluorimetric recording of angiotensin II-induced calcium signals employing a dominant negative knockdown strategy.TRPC3 immunoreactivity was observed in surface plasma membrane regions and in an intracellular membrane system. Co-immunolabeling of TRPC3 and NCX1 indicated significant co-localization of the two proteins. Both co-immunoprecipitation and GST-pulldown experiments demonstrated association of TRPC3 with NCX1. PLC stimulation was found to trigger NCX-mediated Ca2+ entry, which was dependent on TRPC3-mediated Na+ loading of myocytes. This NCX-mediated Ca2+ signaling was significantly suppressed by expression of a dominant negative fragment of TRPC3. PLC stimulation was associated with increased membrane presentation of both TRPC3 and NCX1.These results suggest a PLC-dependent recruitment of a TRPC3-NCX1 complex into the plasma membrane as a pivotal mechanism for the control of cardiac Ca2+ homeostasis.
Significant effects of mild endogenous hormonal changes in humans: considerations for low-dose testing.
Authors: F Brucker-Davis, K Thayer, T Colborn
Journal: Environmental Health Perspectives (2001)

We review the significant and adverse health effects that can occur with relatively small endogenous hormonal changes in pubertal and adult humans. We discuss the effects of hormonal changes that occur within normal physiologic ranges--such as the rising levels of estrogen in peripuberty, which cause growth spurts at low levels and then the fusion of epiphyses at higher levels--and the hormonal variations during the menstrual cycle and their relation to genital phenotypic changes and intercurrent disease evolution. We turn next to adaptive changes in gonadal and other functions during aging, exercise, stress, starvation, and chronic diseases, which can serve as models for the effects of exogenous, hormonally active compounds. Then we review the states of borderline hormonal imbalances such as subclinical (having few or very mild symptoms, if any) hypothyroidism or hyperthyroidism, glucose intolerance, and other endocrine conditions. Finally, we review the deleterious systemic effects of gonadal imbalance. Information stemming from clinical observations leads to the concept of "no threshold" within the endocrine system and thus illustrates the importance of considering low-dose testing for chemicals that interfere with hormonal activity. We also urge attention to more sensitive, less visible end points such as osteoporosis, increased risk for cardiovascular disease, or cognitive changes.
Abstract 4501: Development and biological annotation of a novel RAF inhibitor amenable for clinical evaluation against BRAF (V600E)-harboring human tumors
Authors: Chang-Rung Chen, Jean-Marc Lapierre, Jeffrey D. Szwaya, Yanbin Liu, Nivedita Namdev, Deirdre Lowe, Ron E. Savage, Cathy O. Bull, Thomas C K Chan, Mark A. Ashwell, Dennis S. France
Journal: Cancer Research (2010)

Abstract An activating somatic mutation in BRAF kinase (V600E) is found in approximately 70% of melanomas, 50% of papillary thyroid cancers and 10% of colon cancers, fueling interest in BRAF (V600E) as a therapeutic target for cancer treatment. We have previously described a novel class of RAF inhibitors with initial pre-clinical profiling. This compound class has been optimized for solubility, eADME properties, and oral bioavailability. ARQ 736 has been selected as a candidate to advance into clinical testing. ARQ 736 is a potent RAF inhibitor (IC50 values of 2.6, 2.7, and 7.3 nM against BRAF, BRAF (V600E) and c-Raf-1, respectively) and extremely selective biochemically, with only 11 of 272 human kinases being inhibited within 100-fold of the IC50 against BRAF. Worthy of note, ARQ 736 was also found to be inactive against vascular endothelial growth factor receptor 2 (VEGFR2 or KDR). Despite being a pan-RAF inhibitor, at the cellular level, ARQ 736 showed a high degree of selectivity against cancer cells harboring at least one allele of BRAF (V600E) (IC50 values in cytotoxicity assays of 200-300 nM), while sparing normal cells with wild-type (wt) BRAF and wt ras as well as cancer cells harboring k-ras mutations (IC50 values in cytotoxicity assays ranging from 4 μM to greater than 10 μM). In cellular pharmacodynamic assays, ARQ 736 inhibited the MAPK pathway potently in a rapid and durable fashion (78, 65, and 11 nM respectively for inhibition of ERK phosphorylation in the human melanoma lines A375, SK-MEL-28, and Colo-205). Acute pharmacodynamic studies in vivo showed a nearly complete reduction of phospho-MEK and phospho-ERK in A375 human melanoma tumors grown in athymic xenograft models and significant tumor growth inhibition was shown in the same model with daily dosing of ARQ 736. ARQ 736 was found to be well-tolerated and orally bioavailable in dogs, and has been advanced into full pre-clinical toxicology studies, data from which will be discussed. In summary, ARQ 736 is the advanced candidate of a novel class of BRAF kinase inhibitors with excellent drug-like properties that may have clinical utility for human cancers driven by oncogenic BRAF (V600E). 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 4501.
Potential Complications of High-Dose Epinephrine
Authors: Jerome L. Fleg
Journal: JAMA (1991)

<h3>To the Editor.</h3> — Two interesting studies<sup>1,2</sup>in<i>JAMA</i>compare the efficacy of standard- and high-dose epinephrine in patients undergoing cardiopulmonary resuscitation. In the retrospective study of Callaham et al,<sup>1</sup>the outcome and complication rates were similar in the standard- and high-dose groups. In general, the two groups had similar baseline characteristics. One noteworthy baseline difference, however, was the higher mean age of the high-dose group (69 vs 60 years;<i>P</i>&lt;.05). In the study by Paradis et al,<sup>2</sup>in patients who remained in cardiac arrest after receiving standard-dose epinephrine, high-dose epinephrine caused a substantially greater increase in coronary perfusion pressure (11.3 ± 10.0 mm Hg) than did standard-dose therapy (3.7±5.0 mm Hg). Although the mean age in this study was 58 ± 15 years, the efficacy of epinephrine in raising coronary perfusion pressure was not analyzed by age. Multiple studies in animals and humans have shown
Abstract 2844: Systems biology analysis of tumor and stromal genes in different metastatic microenvironments
Authors: Lisa Sevenich, Steve Mason, Franck Rapaport, Joan Massague, Christina Leslie, Johanna Joyce
Journal: Cancer Research (2011)

Abstract Metastasis is a multistage process that requires cancer cells to escape from the primary tumor, survive in the circulation, seed at distant sites and colonize these foreign tissue environments. Each of these processes involves rate-limiting steps that are influenced by stromal cells of the tumor microenvironment. Our goal is to dissect organ-site specific signatures of tumor-stroma interactions in metastasis. In this approach we devised an experimental and computational strategy to enable the simultaneous analysis of tumor and stromal genes in lesions from three distinct metastatic microenvironments. We took advantage of a recently developed system where organ-site specific metastatic variants were selected in vivo from a parental breast cancer cell line and home to the brain, the bone and the lung in xenografted animals. An important technological advance is the HuMu ProtIn (Protease/Inhibitor) array that was designed to distinguish between human (Hu) and mouse (Mu) gene expression. By using the HuMu ProtIn array we can determine whether differentially expressed proteases and endogenous protease inhibitors are of tumor (human) or stromal (mouse) origin. This allowed us to simultaneously capture the tumor and stromal contributions in intact tumors. After profiling of brain, bone and lung metastases at different stages of development we employed knock-down and knock-out strategies to experimentally validate the biological relevance of predicted candidate genes including the serine protease Htra1 and the cysteine protease cathepsin S. Cathepsin S represents an interesting example as the expression of tumor-derived cathepsin S decreases during the progression from early to late brain metastasis, whereas the expression of stromal-derived cathepsin S increases over time. Targeting either tumor- or stromal derived cathepsin S did not significantly prolong tumor-free survival, however the combined ablation of tumor- and stromal derived cathepsin S resulted in a dramatic impairment of brain metastasis formation. This study emphasizes the need for a better understanding of the complex reciprocal interactions between tumor cells and stromal cells with the ultimate goal to improve the predictive value of prognostic evaluation and to develop combination therapies that target the tumor along with its microenvironment. 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 2844. doi:10.1158/1538-7445.AM2011-2844
Key Function of Cadherin-Like 26 in Eosinophilic Gastrointestinal Disorders
Authors: Julie M. Caldwell, Margaret Collins, Carine Blanchard, Emily Stucke, Katherine Kemme, Lissa Amin, Philip Putnam, James Franciosi, Juan Pablo Pablo Abonia, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2013)
Use of a Physiologically Based Pharmacokinetic Model for Rats to Study the Influence of Body Fat Mass and Induction of CYP1A2 on the Pharmacokinetics of TCDD
Authors: Claude Emond, Linda S. Birnbaum, Michael J. DeVito
Journal: Environmental Health Perspectives (2006)

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly lipophilic chemical that distributes into adipose tissue, especially at low doses. However, at high doses TCDD sequesters in liver because it induces cytochrome P450 1A2 (CYP1A2) that binds TCDD. A physiologically based pharmacokinetic (PBPK) model was developed that included an inducible elimination rate of TCDD in the Sprague-Dawley rat. Objectives of this work were to characterize the influence of induction of CYP1A2 and adipose tissue mass fraction on the terminal elimination half-life (t1/2) of TCDD using this PBPK model. When the model assumes a fixed elimination of TCDD, t1/2 increases with dose, due to hepatic sequestration. Because experimental data indicate that the t1/2 of TCDD decreases with dose, the model was modified to include an inducible elimination rate. The PBPK model was then used to compare the t1/2 after an increase of adipose tissue mass fraction from 6.9 to 70%. The model suggests that at low exposures, increasing adipose tissue mass increases the terminal t1/2. However, at higher exposures, as CYP1A2 is induced, the relationship between adipose tissue mass and t1/2 reaches a plateau. This demonstrates that an inducible elimination rate is needed in a PBPK model in order to describe the pharmacokinetics of TCDD. At low exposures these models are more sensitive to parameters related to partitioning into adipose tissue.
Letter by Rosenstein and Parra Regarding Article, “Greater Clinical Benefit of More Intensive Oral Antiplatelet Therapy With Prasugrel in Patients With Diabetes Mellitus in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel: Thrombolysis in Myocardial Infarction 38”
Authors: Robert S. Rosenstein, David Parra
Journal: Circulation (2009)
The Effect of Continuous Subcutaneous Insulin Infusion on Endogenous Insulin Secretion in Type I Diabetes
Authors: Angel Pietri, Marilyn Alford, Philip Raskin
Journal: Diabetes Care (1982)

In an attempt to elucidate possible mechanisms for the success of continuous subcutaneous insulin infusion (CSII), we evaluated the C-peptide response to a standard breakfast in seven type I diabetic patients while they were on conventional insulin treatment and again after 4 wk of near-normal glycemia achieved with CSII. While on conventional therapy their 24-h mean blood glucose level was 211 ± 12 mg/dl and their glycosylated hemoglobin level was 10.6 ± 0.6%. After 4 wk of CSII their 24-h mean blood glucose level fell to 95 ± 7 mg/dl and their glycosylated hemoglobin level fell to 6.5 ± 0.4%. Plasma C-peptide levels were undetectable in all seven patients both while on conventional therapy and after 4 wk of CSII. We conclude that the success of CSII is related to an improved method of insulin delivery and not to either the selection of type I diabetic patients who have some residual insulin secretory capacity or to some change in endogenous insulin secretion produced by the treatment itself.
Efficacy of safety of therapy with interferon ALFA-2A+ ribavirin in HIV/HCV coinfected patients. Preliminary results of an open prospective study
Authors: J.A. Galeras, C. Tural, L. Force, S. Montoliu, J.A. Rodriguez de Castro, S. Coll, D. Fuster, P. Barrufet, M.D. Dominguez, R. Planas, R. Sola
Journal: Journal of Hepatology (2003)
Rubella Arthritis
Authors: Robert E. Johnson, Arthur P. Hall
Journal: New England Journal of Medicine (1958)

An interesting, self-limited form of polyarthritis that follows rubella (German measles) has often been described in the foreign literature but seldom mentioned in this country. Apparently, at least in New England,1 this complication is not rare, and a recent study of 10 such cases served to call attention to this fact.Young adults, predominantly females,2 , 3 are most commonly reported to have this complication. Joint pains, with swelling, appear with or shortly after the onset of the rash and last a few days to a week. In some cases a secondary rise in temperature to 102 or 103°F. occurs with the . . .
Author's reply to Lichtenstein, Tedstone and Pyne, Mann and colleagues, Lim, and Clifton
Authors: A. Malhotra
Journal: BMJ (2013)

Saturated fat is known to increase low density lipoprotein (LDL)-cholesterol. However, unlike carbohydrates, saturated fat also raises high density lipoprotein (HDL)-cholesterol and reduces triglycerides, with little effect on total cholesterol:HDL ratio—thought to be a better predictor of coronary heart disease (CHD) events than total cholesterol alone.1 2 

The food source of saturated fat may be more important. A recent multi-ethnic study found that high intake of dairy saturated fat was associated with a lower CVD risk but high meat intake …
P866 EVEROLIMUS-BASED IMMUNOSUPPRESSION PROVIDES SUPERIOR RENAL FUNCTION AND COMPARABLE EFFICACY VERSUS STANDARD TACROLIMUS IN DE NOVO LIVER TRANSPLANTATION: 3-YEAR RESULTS FROM H2304 STUDY EXTENSION
Authors: F. Saliba, G.M. Kaiser, L. De Carlis, H.J. Metselaar, P. De Simone, C. Duvoux, F. Nevens, L. Fischer, J. Fung, G. Dong, B. Rauer, G. Junge
Journal: Journal of Hepatology (2014)
Vesico-bullous Diseases Affecting the Eye
Authors: A. Carleton
Journal: BMJ (1949)

ABSTRACT. End-stage renal disease (ESRD) patients treated with hemodialysis have a high mortality rate, which is largely due to inadequate dialysis. Dialysis adequacy, measured by the urea reduction ratio (URR), tends to be correlated within dialysis facilities with wide variations in average center adequacy. These are characteristics of a center effect, which can have an important impact on dialysis adequacy. This study measured the center effect observed in an ESRD Network before and after a successful quality improvement project (QIP). URR values were recorded on patients sampled from 196 facilities in ESRD Network 6 before (pre-QIP, <i>n</i> = 5309) and after (post-QIP, <i>n</i> = 5753). These data was used to determine the <i>within center</i> correlation (ρ) of individual URR values and <i>between center</i> variation in aggregate URR values in both samples. The overall mean URR improved from the pre- to post-QIP sample (mean URR 64.7 ± 0.1 <i>versus</i> 69.8 ± 0.1, respectively; <i>P</i> = 0.001). There was a high degree of <i>within center</i> correlation in dialysis adequacy across the facilities, which significantly diminished post-QIP (ρ, 0.15 [95% CI, 0.12 to 0.18] <i>versus</i> ρ, 0.06 [95% CI, 0.04 to 0.08]). The <i>between center</i> variation in mean URR also declined from the pre-QIP to the post-QIP sample (SD, 3.6 <i>versus</i> 2.8). In conclusion, there is a center effect on dialysis adequacy measurable in an ESRD Network, which diminishes after a successful QIP; therefore, when implementing a QIP to improve dialysis adequacy, changes in the center effect should be considered a potential indicator of the efficacy of the intervention.
Cervical screening in the inner cities: is the opportunistic approach still worthwhile?
Authors: H. Stirland, O A N Husain, E B. Butler, S. Cater, K. S. Russell
Journal: BMJ (1996)

Since the national call and recall cervical screening programme was set up in 1988, population coverage has improved.1 Geographical differences persist, however, and many inner city areas have a 40-60% response rate.2 Factors associated with low acceptance rates for screening include unemployment, overcrowding, ethnic minority, population mobility, and inaccuracy of the patient registers of family health services authorities.3 Also, women may not perceive themselves to be at risk or may not wish to attend their doctor's surgery or the local clinic.

The inner London Borough of Wandsworth has a multicultural population of all social classes. In 1992-3 the uptake of cervical screening was 60%. The Women's Nationwide Cancer Control Campaign (WNCCC) has over 25 years' experience in providing mobile units for both public and workplace screening, which have been shown to improve …
rHuEPO enhances the production of plasminogen activator inhibitor-1 in cultured endothelial cells
Authors: Tetsushi Nagai, Tadao Akizawa, Shiho Kohjiro, Fumihiko Koiwa, Kunihiro Nabeshima, Kazuhiko Niikura, Kyoko Kino, Naoaki Kanamori, Eriko Kinugasa, Terukuni Ideura
Journal: Kidney International (1996)
Pulmonary metastatic calcification with respiratory insufficiency in patients on maintenance haemodialysis.
Authors: E Justrabo, R Genin, G Rifle
Journal: Thorax (1979)

A uraemic patient undergoing chronic haemodialysis developed diffuse metastatic pulmonary calcification and died from acute respiratory insufficiency after renal transplantation. Thirteen similar cases previously published are reviewed, with emphasis on the clinical and anatomical features of such calcinosis. The pathogenesis of this calcification in patients on maintenance haemodialysis and some rules for its prevention are discussed.