tbuckley/cabot-search huggingface dataset:
Brief Therapy of Conversion Reactions: An In-Hospital Technique
Authors: RICHARD A. DICKES
Journal: American Journal of Psychiatry (1974)

This paper describes a treatment method for conversion phenomena, reactions that present special technical difficulties. The strategy focuses the patient's attention on the fact that his symptoms are psychologically motivated and reduces opportunity for secondary gain. The author reports data from a clinical trial in which the special treatment regimen was compared with a variety of other treatment methods; he cautions that early identification and treatment are necessary to prevent the symptom complex from becoming a permanent feature of the patient's mental life.
Taking advantage of saliva
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

The bacterium Anaplasma phagocytophilum uses a tick protein to help it set up camp in the insect's salivary glands, according to Sukumaran and colleagues (page 1507).






Figure 1

A disease-causing bacterium uses a tick (shown) salivary protein to establish infection in the insect's salivary glands.




Many tick-borne pathogens hijack host proteins to establish infection in their tick vector or mammalian host. Previous work by this group, for example, showed that the Lyme disease bacterium Borrelia burgdorferi induces the expression of the salivary protein Salp15 in infected Ixodes scapularis ticks as they feed. The bacterium then coats itself with Salp15 as it exits the tick, creating a shield against the destructive antibodies encountered in the mammalian host.

Here, Sukumaran and colleagues used a similar approach to study the obligate intracellular bacterium A. phagocytophilum, which causes a common and sometimes deadly tick-borne disease in humans called anaplasmosis (formerly granulocytic ehrlichiosis). They found that if I. scapularis ticks fed on A. phagocytophilum–infected mice, the ticks selectively increased their expression of the salivary protein Salp16.

But in this case, Salp16 was used for protection in the tick, not the mammalian host. Inhibiting Salp16 expression in the tick (using RNAi) reduced the number of bacteria in the insect's salivary glands, suggesting that Salp16 was needed for the bacterium to establish a foothold in the salivary gland where it resides after migrating from the gut. Once there, however, the bug no longer required Salp16 to maintain its residence. Inhibiting Salp16 had no effect on transmission of the bug to the mouse reservoir or on the initial uptake of the bug (with the blood meal) into the tick gut.

The authors are now trying to determine how Salp16 helps A. phagocytophilum to colonize the salivary gland. In the meantime, blocking Salp16 in ticks might provide a way to disrupt the transmission cycle of the pathogen and thus lower the prevalence of disease.
Effects of Intraduodenal Glutamine on Incretin Hormone and Insulin Release, the Glycemic Response to an Intraduodenal Glucose Infusion, and Antropyloroduodenal Motility in Health and Type 2 Diabetes
Authors: Jessica Chang, Tongzhi Wu, Jerry R. Greenfield, Dorit Samocha-Bonet, Michael Horowitz, Christopher K. Rayner
Journal: Diabetes Care (2013)

Glutamine reduces postprandial glycemia when given before oral glucose. We evaluated whether this is mediated by stimulation of insulin and/or slowing of gastric emptying.Ten healthy subjects were studied during intraduodenal (ID) infusion of glutamine (7.5 or 15 g) or saline over 30 min, followed by glucose (75 g over 100 min), while recording antropyloroduodenal pressures. Ten patients with type 2 diabetes mellitus (T2DM) were also studied with 15 g glutamine or saline.ID glutamine stimulated glucagon-like peptide 1 (GLP-1; healthy: P < 0.05; T2DM: P < 0.05), glucose-dependent insulinotropic polypeptide (GIP; P = 0.098; P < 0.05), glucagon (P < 0.01; P < 0.001), insulin (P = 0.05; P < 0.01), and phasic pyloric pressures (P < 0.05; P < 0.05), but did not lower blood glucose (P = 0.077; P = 0.5).Glutamine does not lower glycemia after ID glucose, despite stimulating GLP-1, GIP, and insulin, probably due to increased glucagon. Its capacity for pyloric stimulation suggests that delayed gastric emptying is a major mechanism for lowering glycemia when glutamine is given before oral glucose.
Subepithelial Myofibroblasts Express Cyclooxygenase-2 in Colorectal Tubular Adenomas
Authors: Patrick A. Adegboyega, Omiyosoye Ololade, Jamal Saada, Randy Mifflin, John F. Di Mari, Don W. Powell
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Recent data support the hypothesis that the inducible isoform of cyclooxygenase (COX-2) plays a role in the early stages of colonic carcinogenesis and that nonsteroidal anti-inflammatory drugs (NSAIDs) retard the development of colon cancer by modulating COX-2. However, the cell types responsible for producing COX-2 in colorectal adenomas remain a subject of controversy. Experimental Design: COX-2 expression in normal colonic mucosa (n = 50), hyperplastic polyps (n = 43), sporadic adenomas (n = 67), and invasive colonic adenocarcinoma (n = 39) was studied in formalin-fixed and paraffin-embedded tissue sections from endoscopy biopsy and colonic resection specimens. Immunohistochemistry (avidin-biotin complex technique with double immunolabeling) was used to identify the phenotypes of COX-2-producing cells. Results: In colorectal adenomas, increased expression of COX-2 was detected and localized to α smooth muscle actin (∝SMA)-positive subepithelial stromal cells (myofibroblasts) in the periluminal region of the lamina propria in 63 (94%) of 67 cases. In contrast, in normal colonic mucosa and in hyperplastic polyps with intact epithelium, COX-2 expression was found only in macrophages and endothelial cells. In areas in which the surface epithelium was ulcerated in normal mucosa as well as hyperplastic or neoplastic polyps, COX-2 expression was increased in granulation tissue (and present in macrophages, endothelium, and myofibroblasts). In invasive carcinoma, COX-2 expression in myofibroblasts was limited to the adenomatous portion of the tumor and was detected in 62% of cases (n = 39). In addition, focal expression of COX-2 by malignant epithelial cells was observed in 23% of invasive adenocarcinoma. Conclusions: These results show that increased COX-2 expression in sporadic adenoma of the colon is common and is localized specifically to subepithelial intestinal myofibroblasts. These findings further support the hypothesis that myofibroblasts are important target cells for NSAID-mediated chemoprevention of colorectal cancer.
Antral gastrin-producing G-cells and somatostatin-producing D-cells in different states of gastric acid secretion.
Authors: R Arnold, M V Hulst, C H Neuhof, H Schwarting, H D Becker, W Creutzfeldt
Journal: Gut (1982)

The number of G- and D-cells per area and the ratio of G/D-cells were investigated in biopsy specimens of the pyloric antrum from normochlorhydric subjects without peptic ulcer, from patients with duodenal ulcer, gastrinoma, pernicious anaemia, and after selective proximal vagotomy. Compared with normochlorhydric subjects antral G-cell density was significantly raised in pernicious anaemia, unchanged in duodenal ulcer, and diminished in gastrinoma patients. After vagotomy G-cell density was found to be raised if compared with patients with duodenal ulcer. D-cell density was significantly increased in gastrinoma patients, unchanged in duodenal ulcer, and diminished in pernicious anaemia and after vagotomy. The G/D-cell ratio was increased in pernicious anaemia and after vagotomy, unchanged in duodenal ulcer, and decreased in gastrinoma patients. It is concluded that the antral pH governs the ratio of G- and D-cells. Therefore, the G/D cell ratio increases in states of reduced acid secretion and decreases in massive hyperchlorhydria. Hypergastrinaemia as such does not affect the G/D-cell ratio.
Peripheral vascular disease in patients with systemic lupus erythematosus.
Authors: J McDonald, J Stewart, M B Urowitz, D D Gladman
Journal: Annals of the Rheumatic Diseases (1992)

Patients with systemic lupus erythematosus may develop premature atherosclerosis, notably coronary artery disease. A group of 10 patients with peripheral vascular disease presenting with intermittent claudication or gangrene were studied from a group of 563 patients followed prospectively at the Wellesley Hospital Lupus Clinic. These 10 patients were compared with the next lupus clinic patient matched for age and sex, with respect to demographic characteristics and risk factors. The patients and controls did not differ significantly in lupus activity criteria count, partial thromboplastin time, the number with antibody to cardiolipin, number receiving steroids or mean steroid dose, family history of atherosclerosis, hyperlipidaemia, smoking, hypertension or use of oral contraceptives. The risk factors for developing peripheral vascular disease were a longer duration of systemic lupus erythematosus and a longer duration of use of steroids. Eight of the 10 patients had coexistent coronary artery disease or transient ischaemic attack.
Assessing Women at High Risk of Breast Cancer: A Review of Risk Assessment Models
Authors: E. Amir, O. C. Freedman, B. Seruga, D. G. Evans
Journal: JNCI Journal of the National Cancer Institute (2010)

Women who are at high risk of breast cancer can be offered more intensive surveillance or prophylactic measures, such as surgery or chemoprevention. Central to decisions regarding the level of prevention is accurate and individualized risk assessment. This review aims to distill the diverse literature and provide practicing clinicians with an overview of the available risk assessment methods. Risk assessments fall into two groups: the risk of carrying a mutation in a high-risk gene such as BRCA1 or BRCA2 and the risk of developing breast cancer with or without such a mutation. Knowledge of breast cancer risks, taken together with the risks and benefits of the intervention, is needed to choose an appropriate disease management strategy. A number of models have been developed for assessing these risks, but independent validation of such models has produced variable results. Some models are able to predict both mutation carriage risks and breast cancer risk; however, to date, all are limited by only moderate discriminatory accuracy. Further improvements in the knowledge of how to best integrate both new risk factors and newly discovered genetic variants into these models will allow clinicians to more accurately determine which women are most likely to develop breast cancer. These steady and incremental improvements in models will need to undergo revalidation.
Christmas at Davos Platz
Authors: C. T. Williams
Journal: BMJ (1879)

does, upon loss of blood, although this is certainly one important factor in it.As the blood-vessels must be secured with all possible promptitude, torsion of the arteries is scarcely, I think, applicable, as it requires more time than the ligature.It is better to apply forceps in quick -suc- cession to all bleeding points, and afterwards ligature them.I tied the femoral artery and vein with silk, and the other vessels with catgut, and cut the ends off short.All bleeding veins were tied.It saves loss of blood at the time of operation, and diminishes the chance of subsequent oozing of blood into the cavity of the stump, and is in no respect hurtful in itself.The catgut sutures, inserted very deeply into the flaps to bring their surfaces well into contact, required no subsequent extraction.The ex- ternal portions, with the knot, were dried up, and were picked off the surface in three to four days.The deep loops were no more seen ; there was not a trace of inflammation or irritation around the points of emergence of the sutures.The drawing accurately represents the form and condition of the stump eight weeks after the operation.'/ '.~~~A '~~~~~~~~~~~~~~~~I , "!The operation, severe though it be, was justified by the relief from pain which the patient has received, although the probability of a speedy return of the disease in some internal organ or part is only too likely.No clue is given by this case as to the possible origin of these deadly growths.This young man had been, to all appearance, thoroughly healthy himself, and his father and mother were the same.There was not even an injury which might be alleged as an exciting cause.The supposed obscure connection or interdependence between sarcoma and syphilis, or tubercle, has yet to be proved.
Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma
Authors: Guangwu Guo, Yaoting Gui, Shengjie Gao, Aifa Tang, Xueda Hu, Yi Huang, Wenlong Jia, Zesong Li, Minghui He, Liang Sun, Pengfei Song, Xiaojuan Sun, Xiaokun Zhao, Sangming Yang, Chaozhao Liang, Shengqing Wan, Fangjian Zhou, Chao Chen, Jialou Zhu, Xianxin Li, Minghan Jian, Liang Zhou, Rui Ye, Peide Huang, Jing Chen, Tao Jiang, Xiao Liu, Yong Wang, Jing Zou, Zhimao Jiang, Renhua Wu, Song Wu, Fan Fan, Zhongfu Zhang, Lin Liu, Ruilin Yang, Xingwang Liu, Haibo Wu, Weihua Yin, Xia Zhao, Yuchen Liu, Huanhuan Peng, Binghua Jiang, Qingxin Feng, Cailing Li, Jun Xie, Jingxiao Lu, Karsten Kristiansen, Yingrui Li, Xiuqing Zhang, Songgang Li, Jian Wang, Huanming Yang, Zhiming Cai, Jun Wang
Journal: Nature Genetics (2011)
Drug Transporters in the Central Nervous System: Brain Barriers and Brain Parenchyma Considerations
Authors: Gloria Lee, Shannon Dallas, Meera Hong, Reina Bendayan
Journal: Pharmacological Reviews (2001)

Drug transport in the central nervous system is highly regulated not only by the blood-brain and the blood-cerebrospinal fluid barriers but also in brain parenchyma. The novel localization of drug transporters in brain parenchyma cells, such as microglia and astrocytes, suggest a reconsideration of the present conceptualization of brain barriers as it relates to drug transport. That is, the cellular membranes of parenchyma cells act as a second "barrier" to drug permeability and express transporters whose properties appear similar to those localized at the conventional brain barriers. This review will focus on the molecular characteristics, localization, and substrate specificities of several classes of well known membrane drug transporters (i.e., the organic cation, organic anion, nucleoside, P-glycoprotein, and multidrug resistance proteins) in the brain. Comparisons to similar transporters localized within the peripheral system and clinical implications of the functional expression of specific drug transport families will be discussed when appropriate. Nutrient and neurotransmitter transporters, whose characteristics have been reviewed extensively elsewhere, will not be considered in this review.
Comparative effects of beta adrenergic blocking drugs.
Authors: E Sowton, D S Das Gupta, I Baker
Journal: Thorax (1975)

Although many different beta blockers are now in clinical use, there is very little information concerning their relative efficacy, and it is still not clear what clinical importance should be attached to properties such as positive inotropic stimulation (intrinsic sympathomimetic activity or ISA) and membrane stabilizing action ("local anaesthetic effect" or "quinidine-like effect"). In this report we compare the ability of patients with angina to exercise on a bicycle ergometer while receiving a series of commonly used beta blockers, and attempt to determine the importance of ISA. The investigation is in four parts with the drugs given orally or intravenously: statistical analysis of the results was carried out using standard methods, both parametric and non-parametric (Friedmann analysis of variance, Wilcoxon matched pairs signed ranks test) by two independent statisticians. The relevant properties of drugs included in this paper are summarized in Table I. Laboratory reports using many different animal preparations may differ from this assessment under specific conditions, and the Table is intended only as a guide to the generally accepted properties of these drugs when used clinically. Results for sotalol are included for reference in the first part of this paper but the drug was withdrawn from clinical use and was not studied further.
553 LIVER TRANSPLANTATION FOR HEPATITIS B VIRUS BACKGROUND HEPATOCELLULAR CARCINOMA: A PROSPECTIVE STUDY COMPARING MILAN AND HANGZHOU CRITERIA AT A SINGLE TRANSPLANTATION CENTER IN CHINA
Authors: T. Gao, Q. Li, S. Wang, Y. Feng, J. Chi, S. Chen, Y. Qiu, Q. Xia, H. Li
Journal: Journal of Hepatology (2011)
p53 Expression in Node-Positive Breast Cancer Patients: Results from the Cancer and Leukemia Group B 9344 Trial (159905)
Authors: Jonathan F. Lara, Ann D. Thor, Lynn G. Dressler, Gloria Broadwater, Ira J. Bleiweiss, Susan Edgerton, David Cowan, Lori J. Goldstein, Silvana Martino, James N. Ingle, I. Craig Henderson, Larry Norton, Eric P. Winer, Clifford A. Hudis, Matthew J. Ellis, Donald A. Berry, Daniel F. Hayes
Journal: Clinical Cancer Research (2011)

p53 as a prognostic and predictive factor in early-stage breast cancer has had mixed results. We studied p53 protein expression, by immunohistochemistry, in a randomized clinical trial of stage II patients treated with adjuvant doxorubicin and cyclophosphamide with or without paclitaxel [Cancer and Leukemia Group B (CALGB) 9344, INT0148].
Malignant neoplasms in pulmonary sarcoidosis
Authors: J. M REICH;, N SEERSHOLM, J VESTBO, K VISKUM
Journal: Thorax (1998)

As its authors intended—by limiting their analysis of the association to instances in which recognition of malignancy succeeded a diagnosis of sarcoidosis by more than one year—the study by Seersholm et al 1 rigorously tested the hypothesis proposed by ‖Brincker and Wilbek2that persons with respiratory sarcoidosis are predisposed to develop malignancies. Several …
Targeting tumor-necrosis factor receptor pathways for tumor immunotherapy
Authors: David A Schaer, Daniel Hirschhorn-Cymerman, Jedd D Wolchok
Journal: Journal for ImmunoTherapy of Cancer (2014)

With the success of ipilimumab and promise of programmed death-1 pathway-targeted agents, the field of tumor immunotherapy is expanding rapidly. Newer targets for clinical development include select members of the tumor necrosis factor receptor (TNFR) family. Agonist antibodies to these co-stimulatory molecules target both T and B cells, modulating T-cell activation and enhancing immune responses. <i>In vitro</i> and <i>in vivo</i> preclinical data have provided the basis for continued development of 4-1BB, OX40, glucocorticoid-induced TNFR-related gene, herpes virus entry mediator, and CD27 as potential therapies for patients with cancer. In this review, we summarize the immune response to tumors, consider preclinical and early clinical data on select TNFR family members, discuss potential translational challenges and suggest possible combination therapies with the aim of inducing durable antitumor responses.
Treating acute rheumatic fever
Authors: A. Cilliers
Journal: BMJ (2003)

So many years, and yet we do not know if steroids should be used 

Rheumatic fever is a delayed complication of pharyngeal infection with group β haemolytic streptococci. Susceptible individuals develop a diffuse inflammatory disease of the heart, joints, brain, blood vessels, and subcutaneous tissue. Carditis is the most serious manifestation of the disease. It may culminate in chronic valvular disease and can lead to heart failure and ultimately death. The incidence of acute rheumatic fever has declined in industrialised countries since the 1950s. However, a resurgence of the disease has been noted, and new epidemics have been reported in the United States.1 Acute rheumatic fever continues to be an important cause of acquired heart disease in developing countries where it is an endemic disease.2 Open heart surgery may be needed to repair or replace heart valves in patients with severely damaged …
A Simplified Approach to the Management of Non–ST-Segment Elevation Acute Coronary Syndromes
Authors: Ty J. Gluckman, Molly Sachdev, Steven P. Schulman, Roger S. Blumenthal
Journal: JAMA (2005)

While current practice guidelines provide an evidence-based approach to management of acute coronary syndromes (ACS), application of the evidence by individual physicians has been suboptimal.To assess and synthesize the evidence regarding optimal management of non-ST-segment elevation ACS (NSTE-ACS).Systematic searches of peer-reviewed publications were performed in MEDLINE and the Cochrane Database from January 1990 through November 2004, with consultation by content experts. Search terms included antiplatelet therapy, antithrombotic therapy, angiotensin-converting enzyme inhibition, angiotensin receptor blockade, beta-blockade, hypertension, hyperlipidemia, cigarette smoking, diet, diabetes mellitus, exercise, myocardial ischemia, and coronary artery disease.Criteria for selection of studies included controlled study design, English language, and clinical pertinence. Data quality was based on the publishing journal and relevance to clinical management of NSTE-ACS.While outcomes of controlled studies support a comprehensive approach in the management of patients with NSTE-ACS, many physicians perceive existing guidelines as lengthy and complex. After risk stratification to identify those patients most likely to benefit from an early invasive vs early conservative strategy, a comprehensive management plan can be assembled through an "ABCDE" approach. The elements of this include "A" for antiplatelet therapy, anticoagulation, angiotensin-converting enzyme inhibition, and angiotensin receptor blockade; "B" for beta-blockade and blood pressure control; "C" for cholesterol treatment and cigarette smoking cessation; "D" for diabetes management and diet; and "E" for exercise.An "ABCDE" approach for the management of NSTE-ACS provides a practical and systematic means to implement evidence-based medicine into clinical practice.
Value of routine follow-up procedures for patients with stage I/II cervical cancer treated with combined surgery–radiation therapy
Authors: P. Morice, C. Deyrolle, A. Rey, D. Atallah, P. Pautier, S. Camatte, A. Thoury, C. Lhomme, C. Haie-Meder, D. Castaigne
Journal: Annals of Oncology (2004)