tbuckley/cabot-search huggingface dataset:
ABC of monitoring drug therapy. Why monitor drug therapy?
Authors: J. K. Aronson, M. Hardman
Journal: BMJ (1992)

It is common clinical practice to monitor the response to treatment of a disease.Obvious examples include monitoring the treatment of hypertension by measuring a patient's blood pressure, the course of an infection by measuring body temperature, and asthma by measuring the peak expiratory flow rate.The effects of a drug are not often monitored, however, despite the fact that monitoring techniques are available.In this series we will discuss: * The reasons for monitoring drug treatment * The ways in which therapeutic responses to drugs can be measured * Monitoring patient compliance * Measuring and interpreting plasma drug concentrations as a means ofThe peak expiratory flow rate in monitoring drug treatment.patients with asthma can be used to monitor diurnal variation in airways resistance and the effects of bronchodilators.
Novel FV mutation (W1920R, FVNara) associated with serious deep vein thrombosis and more potent APC resistance relative to FVLeiden
Authors: Keiji Nogami, Keiko Shinozawa, Kenichi Ogiwara, Tomoko Matsumoto, Kagehiro Amano, Katsuyuki Fukutake, Midori Shima
Journal: Blood (2014)
Sphingolipid metabolism: roles in signal transduction and disruption by fumonisins.
Authors: A H Merrill, M C Sullards, E Wang, K A Voss, R T Riley
Journal: Environmental Health Perspectives (2001)

Sphingolipids have important roles in membrane and lipoprotein structure and in cell regulation as second messengers for growth factors, differentiation factors, cytokines, and a growing list of agonists. Bioactive sphingolipids are formed both by the turnover of complex sphingolipids and as intermediates of sphingolipid biosynthesis. Usually, the amounts are highly regulated; however, by inhibiting ceramide synthase, fumonisins block the biosynthesis of complex sphingolipids and cause sphinganine (and sometimes sphingosine) to accumulate. Where the mechanism has been studied most thoroughly, the accumulation of sphingoid bases is a primary cause of the toxicity of fumonisin B (FB). Nonetheless, the full effects of fumonisins probably involve many biochemical events. The elevations in sphingoid bases also affect the amounts of other lipids, including the 1-phosphates and N-acetyl derivatives of sphinganine. Furthermore, the aminopentol backbone of FB1 (AP1) is both an inhibitor and a substrate for ceramide synthase, and the resultant N-palmitoyl-AP1 (PAP1) is an even more potent inhibitor of ceramide synthase (presumably as a product analog). PAP1 is 10 times more toxic than FB1 or AP1 for HT-29 cells in culture, and hence may play a role in the toxicity of nixtamalized fumonisins. All these processes--the effects of fumonisins on sphingolipid metabolism, the pathways altered by perturbation of sphingolipid metabolism, and the complex cellular behaviors regulated by sphingolipids--must be borne in mind when evaluating the pathologic effects of fumonisins.
Genetic Testing: Care, Consent, and Liability
Authors: Alison J. Whelan
Journal: Annals of Internal Medicine (2006)

Medical Writings: Book Notes4 July 2006Genetic Testing: Care, Consent, and LiabilityAlison J. Whelan, MDAlison J. Whelan, MDFrom Washington University School of Medicine, St. Louis, Missouri.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-145-1-200607040-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Sharp NF and Carter RF. 594 pages. New York: Wiley-Liss; 2006. $89.95. ISBN 0471748897. Order at www.wiley.com.Field of medicine: Medical genetics.Format: Hardcover book.Audience: Medical students, residents, and nongeneticist health care providers.Purpose: To discuss the major concepts of genetic diseases, the ethical and legal issues surrounding them, and the special skills needed to provide better care for patients with genetic disease.Content: The book focuses on genetic testing, with an emphasis on counseling issues, a framework for clinical thinking, and the ethical and legal ramifications of testing. Areas of testing discussed range from prenatal testing and newborn ... Author, Article, and Disclosure InformationAffiliations: From Washington University School of Medicine, St. Louis, Missouri. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 July 2006Volume 145, Issue 1Page: 80KeywordsClinical geneticsGenetic counselingGenetic diseasesGenetic testingGeneticsHealth care providersLibrariesMedical geneticsPatientsSoftware tools ePublished: 4 July 2006 Issue Published: 4 July 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Does gene expression analysis inform us in rheumatoid arthritis?
Authors: T Haupl, B Stuhlmuller, A Grutzkau, A Radbruch, G-R Burmester
Journal: Annals of the Rheumatic Diseases (2009)

Transcription profiling has become a standard technology in research. It is mainly applied in the search for biomarkers to improve diagnostic and prognostic classification, to quantify disease activity and to predict or indicate response to therapy. This review will focus on rheumatoid arthritis and discuss considerations for sample selection, prerequisites for functional interpretation of data and the current status of information deduced in the field of biomarkers for the various clinical questions. In the next few years, prediction of response to treatment is the most important aim of biomarker research. With the growing number of new biological agents, there is increasing pressure to identify molecular parameters that will not only guide the therapeutic decision but also help to define the most important targets for which new biological agents should be tested in clinical studies.
Pediatric Alpha-Gal: IgE Antibodies to Galactose-Alpha-1,3-Galactose in Children Presenting with Delayed Urticaria or Anaphylaxis
Authors: Hayley James, Josh L. Kennedy, Thomas Platts-Mills, Amy Polen Stallings, Lisa J. Workman, Anubha Tripathi, Shawna Pochan, Charles Lane, Luis A. Matos, Saju S. Eapen, Dane C. McBride, Peter W. Heymann, Scott P. Commins
Journal: Journal of Allergy and Clinical Immunology (2013)
Abstract P6-08-09: A national survey on oncology clinicians’ recommendations and knowledge of contraception for women with cancer
Authors: SB Giordano, SL York, Y Gosiengfiao, K Smith, J Kiley
Journal: Cancer Research (2013)

Abstract PURPOSE Women with cancer have specific reproductive health needs and often look to their oncology clinicians for recommendations and guidance. This study's purpose was to determine contraceptive knowledge and recommendations of oncology clinicians. METHODS An online survey was emailed to U.S.-based medical and pediatric oncologists and oncologic advanced practice clinicians caring for women age 13-45 years. The primary outcome was regular recommendation to start or continue contraception during cancer treatment. Knowledge of pertinent information on contraception was calculated based on percent correct answers to questions on contraceptive failure rates and safety. RESULTS 18.5% of subjects responded to questionnaires (612 initiated surveys of 3334 requests). Pediatric clinicians constituted the majority of the 577 participants meeting inclusion criteria (pediatric oncologists: 48.7%; pediatric advanced practice clinicians: 38.1%). Most clinicians (81.8%) recommend contraception. The mean contraceptive knowledge score was 47.5% (SD: ±17.6%), with 27.2% answering ≥60% questions correctly. Recommending contraception was associated with rating contraception as important (aOR 3.49, 95% CI: 1.46, 8.38); comfort with contraceptive counseling (aOR 1.77, 95% CI: 1.04, 3.00); regular referral to a gynecologist/women's health care provider (aOR 2.92, 95% CI: 1.44, 5.94); and frequency of patients discussing contraception (aOR 4.21, 95% CI: 1.55, 11.43). Advanced practice nurses/physician assistants were less likely to correctly answer ≥60% of contraceptive knowledge questions (aOR 0.44, 95% CI: 0.27, 0.71). CONCLUSION Oncology clinicians recommend young women with cancer use contraception but lack essential knowledge to provide adequate counseling. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-08-09.
RANK brings Aire into the thymus
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2007)

A group of epithelial cells in the thymus guard against autoimmunity by presenting self-antigens to developing T cells—those T cells that take the bait are then killed. On page 1267, Rossi et al. identify the signaling pathway that creates this epithelial barrier and the cells that activate this pathway.






Figure 1

Lymphoid thymic inducers (green) activate RANK to turn on Aire (red) in thymic cells (blue).




Self-reactive T cells are eliminated when they latch on to self-antigens presented by a small subset of medullary thymic epithelial cells (mTECs). The self-antigens are derived from tissue-restricted proteins whose genes are expressed in the specialized mTECs under the supervision of the transcription factor Aire. Humans and mice that lack Aire develop multiorgan autoimmunity, but the mechanism that turns on Aire in the mTECs was not known.

Rossi et al. now show that Aire is activated in the mTECs through signaling via the TNF family receptor RANK, which is found on mTECs. Mice that lacked RANK failed to develop Aire-expressing mTECs and consequently suffered from autoimmunity. The ligand for RANK, RANKL, was provided by a haemopoietic cell population—the lymphoid tissue inducer (LTi) cells. These cells were previously known to reside in secondary lymphoid tissue. The team now finds that the LTi cells are also present in the thymus.

Not all mTECs express Aire, but whether this exclusivity is due to selective expression of RANK is unclear. The team is now investigating how LTi cell–mediated RANK signaling gets targeted to just a small thymic population.
Nocardia Infection in Heart Transplant Patients
Authors: JAMES A. KRICK
Journal: Annals of Internal Medicine (1975)

Infection due to Nocardia asteroides was observed in seven heart transplant patients in a 22-month period. In six the diagnosis was made during life, and in one a clinically inapparent lesion was discovered at autopsy. Diagnosis during life was made by initial percutaneous lung aspirate in four and by a second lung aspirate in two patients. The infection was confined to the lungs in five cases and disseminated to the skin in two others. In one patient extensive destruction of muscles of the leg due to spread of nocardial infection from an adjacent subcutaneous abscess necessitated amputation of the leg. All the patients were treated with sulfisoxazole. No patient died as a result of the nocardial infection. The aggressive diagnostic approach taken toward these immunologically compromised hosts with pulmonary infection resulted in the rapid diagnosis of Nocardia infection and undoubtedly was instrumental in their survival.
Trial shows vaccine halves malaria episodes in children in Africa
Authors: J. H. Tanne
Journal: BMJ (2011)

An antimalaria vaccine halved the number of first clinical episodes of malaria and severe malaria in children in the 12 months after vaccination, according to results from a clinical trial.

The trial included 6000 children aged 5 to 17 months old when they were enrolled at 11 centres in seven African countries. They were randomised to three doses of the new vaccine at one month intervals or a non-malaria comparator vaccine.

Results in the 14 months after the initial dose of vaccine showed the incidence of clinical malaria was 0.32 episodes per person year in children receiving the antimalaria vaccine compared with 0.55 episodes in the control group. The vaccine’s protection was lower at the end of 12 months, suggesting that a booster may be needed. Adverse events …
Craniopharyngeal Pituitary Gland
Authors: John Nichols
Journal: JAMA (1963)

A patient is described who did not mature and at age 20 had a calcified suprasellar cystic meningioma removed. For the next 24 years he showed all of the signs and symptoms of panhypopituitarism except normal pigmentation. At autopsy, a normal craniopharyngeal pituitary was found encased in bone and separated from the hypothalamus by a callus replacing the meningioma. Complete atrophy of thyroid and gonads indicated that thyrotrophic and gonadotrophic formation had ceased. Partial maintenance of adrenal cortices indicated a slight amount of ACTH was being formed, while normal pigmentation indicated melanotrophic hormone was still being formed in a normal amount.
Nonverbal and Verbal Emotional Expression and Health
Authors: Diane S. Berry, James W. Pennebaker
Journal: Psychotherapy and Psychosomatics (1993)

The spontaneous nonverbal expression of emotion is related to immediate reductions in autonomic nervous system activity. Similar changes in specific autonomic channels occur when individuals are encouraged to verbally express their emotions. Indeed, these physiological changes are most likely to occur among individuals who are either verbally or nonverbally highly expressive. These data suggest that when individuals must actively inhibit emotional expression, they are at increased risk for a variety of health problems. Several experiments are summarized which indicate that verbally expressing traumatic experiences by writing or talking improves physical health, enhances immune function, and is associated with fewer medical visits. Although less research is available regarding nonverbal expression, it is also likely that the nonverbal expression of emotion bears some relation to health status. We propose that the effectiveness of many common expressive therapies (e.g., art, music, cathartic) would be enhanced if clients are encouraged to both express their feelings nonverbally and to put their experiences into words.
Phase III Trial of Capecitabine Plus Oxaliplatin As Adjuvant Therapy for Stage III Colon Cancer: A Planned Safety Analysis in 1,864 Patients
Authors: Hans-Joachim Schmoll, Thomas Cartwright, Josep Tabernero, Marek P. Nowacki, Arie Figer, Jean Maroun, Timothy Price, Robert Lim, Eric Van Cutsem, Young-Suk Park, Joseph McKendrick, Claire Topham, Gemma Soler-Gonzalez, Filipo de Braud, Mark Hill, Florin Sirzén, Daniel G. Haller
Journal: Journal of Clinical Oncology (2006)

To report the results of a planned safety analysis from a phase III trial comparing capecitabine plus oxaliplatin (XELOX) with bolus fluorouracil/leucovorin (FU/LV) as adjuvant therapy for stage III colon cancer.Patients with stage III colon carcinoma were randomly assigned to receive either XELOX (intravenous oxaliplatin plus oral capecitabine; 3-week cycle for eight cycles) or standard intravenous bolus FU/LV administered as the Mayo Clinic (Mayo; Rochester, MN) or Roswell Park (RP; Buffalo, NY) regimen for a similar length of time. A total of 1,886 patients were randomly assigned.The safety population comprised 1,864 patients, of whom 938 received XELOX and 926 received FU/LV. Most treatment-related adverse events (AEs) occurred at similar rates in both treatment arms. However, patients receiving XELOX experienced less all-grade diarrhea, alopecia, and more neurosensory toxicity, vomiting, and hand-foot syndrome than those patients receiving FU/LV. Compared with Mayo, XELOX showed fewer grade 3/4 hematologic AE and more grade 3/4 gastrointestinal AE. Compared with RP, XELOX showed less grade 3/4 gastrointestinal AE and more grade 3/4 hematologic AE. As expected grade 3/4 neurosensory toxicity and grade 3 hand-foot syndrome were higher with XELOX. Treatment-related mortality within 28 days from the last study dose was 0.6% in the XELOX group and 0.6% in the FU/LV group.XELOX has a manageable tolerability profile in the adjuvant setting. Efficacy data will be available within the next 24 months.
Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B.
Authors: C Boni, A Bertoletti, A Penna, A Cavalli, M Pilli, S Urbani, P Scognamiglio, R Boehme, R Panebianco, F Fiaccadori, C Ferrari
Journal: Journal of Clinical Investigation (1998)

High viral and/or antigen load may be an important cause of the T cell hyporesponsiveness to hepatitis B virus (HBV) antigens that is often observed in patients with chronic HBV infection. Reduction of viral and antigen load by lamivudine treatment represents an ideal model for investigating this hypothesis. HLA class II restricted T cell responses and serum levels of HBV-DNA, HBsAg, and HBeAg were studied before and during lamivudine treatment in 12 patients with hepatitis B e antigen positive chronic active hepatitis B to assess possible correlations between viral and/or antigen load and vigor of the T cell response. Cell proliferation to HBV nucleocapsid antigens and peptides and frequency of circulating HBV nucleocapsid-specific T cells were assessed to characterize CD4-mediated responses. A highly significant enhancement of the CD4-mediated response to HBV nucleocapsid antigens was already detectable in most patients 7-14 d after the start of lamivudine treatment. This effect was dramatic and persistent in 10 patients but undetectable in 2. It occurred concomitant with a rapid and marked reduction of viremia. Interestingly, lamivudine also enhanced the responses to mitogens and recall antigens, showing that its effect was not limited to HBV-specific T cells. In conclusion, an efficient antiviral T cell response can be restored by lamivudine treatment in patients with chronic hepatitis B concurrently with reduction of viremia, indicating the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients. Since lamivudine treatment can overcome T cell hyporeactivity, combining lamivudine with treatments directed to stimulate the T cell response may represent an effective strategy to induce eradication of chronic HBV infection.
Nuclear Medicine Evaluation of Focal Fatty Infiltration of the Liver
Authors: MARTIN K. BAKER, DONALD S. SCHAUWECKER, JOSEF C. WENKER, KENYON K. KOPECKY
Journal: Clinical Nuclear Medicine (1986)

Focal fatty infiltration of the liver (FFIL) occasionally may be mistaken as metastatic disease, primary liver malignancy, or other space-occupying lesions on CT or ultrasound studies, especially if there is significant mass effect. In these confusing cases, Xe-133 liver imaging has been advocated for confirmation of FFIL, since such studies have been reported to be sensitive and specific. The authors present results of four Xe-133 and four Tc-99m sulfur colloid scans in six patients with FFIL. Xe-133 imaging was found useful for diagnostic confirmation in only one patient and was misleading in the other three. Routine liver-spleen imaging was a more reliable method of confirmation, since no focal defects were found in any of the patients.
Secretion pattern of secretin in man: regulation by gastric acid.
Authors: O B Schaffalitzky de Muckadell, J Fahrenkrug
Journal: Gut (1978)

Median concentration of plasma secretin in the fasting state in 11 achlorhydria patients, 17 normal subjects, eight duodenal ulcer patients, and 11 Zollinger-Ellison patients was 0.3, 1.2, 2.5, and 5.9 pmol x 1(-1), respectively. Aspiration of gastric acid normal subjects and duodenal ulcer patients was followed by a significant lowering of the plasma secretin concentration. In normal subjects insulin-induced hypoglycaemia resulted in increased secretin levels when gastric acid was allowed to enter the duodenum, whereas no changes were observed when gastric acid was aspirated. Simultaneous measurements of intraduodenal pH and plasma secretin concentration in the fasting state and in response to a meal showed that rapid falls in intraduodenal pH were followed by short-lived increments in plasma secretin concentration. These changes in pH and in secretin levels were diminished after cimetidine. It is concluded that gastric acid in man does trigger release of secretin and that secretin is secreted intermittently both in the fasting state and in response to a meal when boluses of acid enter the duodenum.
Risk of Microsatellite-Unstable Colorectal Cancer Is Associated Jointly with Smoking and Nonsteroidal Anti-inflammatory Drug Use
Authors: Victoria M. Chia, Polly A. Newcomb, Jeannette Bigler, Libby M. Morimoto, Stephen N. Thibodeau, John D. Potter
Journal: Cancer Research (2006)

Abstract Smoking has been consistently associated with an increased risk of colorectal adenomas and hyperplastic polyps as well as colorectal cancer. Conversely, nonsteroidal anti-inflammatory drugs (NSAID) have been associated with reduced colorectal cancer risk. We conducted a population-based case-control study to evaluate the joint association between smoking and regular NSAID use with colorectal cancer risk; we also examined these associations stratified by tumor microsatellite instability (MSI). We analyzed 1,792 incident colorectal cancer cases and 1,501 population controls in the Seattle, Washington area from 1998-2002. MSI, defined as MSI high (MSI-H) or MSI-low/microsatellite stable (MSI-L/MSS), was assessed in tumors of 1,202 cases. Compared with nonsmokers, colorectal cancer risk was modestly increased among individuals who had ever smoked. Current NSAID use was associated with a 30% lower risk compared with nonusers. There was a statistically significant interaction between smoking duration and use of NSAIDs (Pinteraction = 0.05): relative to current NSAID users who never smoked, individuals who had both smoked for &amp;gt;40 years and had never used NSAIDs were at the highest risk for colorectal cancer (adjusted odds ratio, 2.8; 95% confidence intervals, 1.8-4.1). Compared with nonsmokers, there was a stronger association within MSI-H tumors with current smoking than there was within MSI-L/MSS tumors. Smokers of long duration were at elevated risk of MSI-H tumors even with NSAID use. The risk of MSI-L/MSS tumors was not elevated among long-duration smokers with long exposure to NSAIDs but was elevated among long-duration smokers who had never used NSAIDs. There seems to be a synergistic inverse association (implying protection) against colorectal cancer overall as a result of NSAID use and nonsmoking, but risk of MSI-H colorectal cancer remains elevated among smokers even when they have a history of NSAID use. (Cancer Res 2006; 66(13): 6877-83)
AstraZeneca pays $520m fine for off label marketing
Authors: J. H. Tanne
Journal: BMJ (2010)

AstraZeneca agreed to pay a $520m (£340m; €391m) fine to settle allegations it had marketed the antipsychotic drug quetiapine fumarate (Seroquel) for unapproved off label uses, the US Department of Justice announced on 27 April.

The drug was a bestseller for AstraZeneca in 2009, with sales of $4.9bn. Eric Holder, the US attorney general, took the unusual step of announcing the settlement at a news conference. He said that illegal acts by drug companies and false claims for government health programmes “can put the public health at risk, corrupt medical decisions by health care providers, and take …
LATE GADOLINIUM ENHANCED CMR-GUIDED IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR IMPLANTATION TO PREVENT SUDDEN CARDIAC DEATH IN CARDIAC SARCOIDOSIS: A MARKOV ANALYSIS
Authors: Amit V. Patel, Amit K. Mehrotra, Sushil Jain, John F. Beshai, Amit R. Patel
Journal: Journal of the American College of Cardiology (2013)