tbuckley/cabot-search huggingface dataset:
Transplacental Chemical Carcinogenesis in Man
Authors: Robert W. Miller
Journal: JNCI Journal of the National Cancer Institute (1971)

This editorial was prompted by the published association of maternal diethylstilbestrol (DES) ingestion during pregnancy and subsequent development of vaginal adenocarcinoma among female offspring, and explores various factors involved in transplacental chemical carcinogenesis in humans. Known prenatal determinants of carcinogenic transmission are 1) germ cells, 2) transplantation, and 3) ionizing radiation. Other chemicals besides DES which may be implicated in transplacental carcinogenesis are cytotoxic anticancer agents, such as therapy. The hypothesis of DES-associated maternal-fetal exchange was developed as a result of physician recognition of a cluster of cases with commonality; it is hoped that further epidemiological studies, more systemitized, will lead to hypotheses regarding the epidemiology of other in utero carcinogenesis.
Interassociation consensus statement on cardiovascular care of college student-athletes
Authors: Brian Hainline, Jonathan Drezner, Aaron Baggish, Kimberly G Harmon, Michael S Emery, Robert J Myerburg, Eduardo Sanchez, Silvana Molossi, John T Parsons, Paul D Thompson
Journal: British Journal of Sports Medicine (2016)

Cardiovascular evaluation and care of college student-athletes is gaining increasing attention from both the public and medical communities. Emerging strategies include screening of the general athlete population, recommendations of permissible levels of participation by athletes with identified cardiovascular conditions and preparation for responding to unanticipated cardiac events in athletic venues. The primary focus has been sudden cardiac death and the usefulness of screening with or without advanced cardiac screening. The National Collegiate Athletic Association convened a multidisciplinary task force to address cardiovascular concerns in collegiate student-athletes, and to develop consensus for an interassociation statement. This document summarises the task force deliberations and follow-up discussions, and includes available evidence on cardiovascular risk, preparticipation evaluation and the recognition of and response to cardiac arrest. Future recommendations for cardiac research initiatives, education and collaboration are also provided.
Esophageal stricture caused by a mediastinal hamartoma invading the esophageal wall
Authors: Xiao-jun Zhao, Hui Xie, Dong-liang Yu, Jian-qiu Sheng
Journal: Endoscopy (2015)

A 60-year-old man presented with dysphagia, which had persisted for 2 months. A barium meal test revealed a stricture in the upper esophagus, and smooth mucosa at the narrow segment of the esophagus ([Fig. 1]). He subsequently underwent endoscopy. Endoscopic examination revealed a mucosal bulge in the esophagus at a distance of 18 – 24 cm from the incisors, extending to about half of the esophageal wall, and with smooth mucosa at the ridge surface. Narrow-band imaging did not show any abnormality of the mucosal surface ([Fig. 2]). Although the esophagus was narrow, it allowed insertion of the endoscope. Gross endoscopic appearance indicated that the lesion would be firm when touched with biopsy forceps. Biopsy revealed inflammatory granulation tissue, and chest computed tomography showed thickening of the mucosa at the upper esophagus ([Fig. 3]).
Case 45-1978
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Alfred M. Cohen, John C. Long
Journal: New England Journal of Medicine (1978)

Presentation of CaseA 25-year-old man was admitted to the hospital because of abdominal pain.He was well until three months earlier, when he experienced diffuse abdominal cramps that disappeared after several days. Twenty-five days before admission abdominal cramps recurred and were most prominent several hours after meals; he passed loose stools, without blood or mucus. Three weeks before entry alternating diarrhea and constipation developed, with upper abdominal and periumbilical pain accompanied by nausea. The hematocrit was 45 per cent, and the white-cell count 6000. An automated scan of 12 blood-chemistry determinations was reported to be normal. A stool specimen . . .
Views of practicing psychiatrists on the treatment of anxiety and somatoform disorders
Authors: G Andrews, D Hadzi-Pavlovic, H Christensen, R Mattick
Journal: American Journal of Psychiatry (1987)

Psychiatrists in Australia were asked to recommend treatments for several anxiety and somatoform disorders. In previous surveys they had agreed about the preferred treatments for schizophrenia and major affective disorder but not about treatments for "neurotic depression" or agoraphobia. In the present survey, no treatment was regarded as critical by a majority of psychiatrists for any of the five anxiety and somatoform disorders studied. The authors conclude that because neurotic disorders form an important part of the workload of psychiatrists, consensus procedures should be used to develop guidelines for treatment until the research literature can provide more adequate guidance.
Early onset combined immunodeficiency and autoimmunity in patients with loss-of-function mutation in <i>LAT</i>
Authors: Baerbel Keller, Irina Zaidman, O. Sascha Yousefi, Dov Hershkovitz, Jerry Stein, Susanne Unger, Kristina Schachtrup, Mikael Sigvardsson, Amir A. Kuperman, Avraham Shaag, Wolfgang W. Schamel, Orly Elpeleg, Klaus Warnatz, Polina Stepensky
Journal: The Journal of Experimental Medicine (2016)

The adapter protein linker for activation of T cells (LAT) is a critical signaling hub connecting T cell antigen receptor triggering to downstream T cell responses. In this study, we describe the first kindred with defective LAT signaling caused by a homozygous mutation in exon 5, leading to a premature stop codon deleting most of the cytoplasmic tail of LAT, including the critical tyrosine residues for signal propagation. The three patients presented from early childhood with combined immunodeficiency and severe autoimmune disease. Unlike in the mouse counterpart, reduced numbers of T cells were present in the patients. Despite the reported nonredundant role of LAT in Ca2+ mobilization, residual T cells were able to induce Ca2+ influx and nuclear factor (NF) κB signaling, whereas extracellular signal-regulated kinase (ERK) signaling was completely abolished. This is the first report of a LAT-related disease in humans, manifesting by a progressive combined immune deficiency with severe autoimmune disease.
The role of empiric embolization in diverticular bleeding
Authors: Chidambaram Valliappan, Ali Kazemi, Michael Babich
Journal: Endoscopy (2015)

A 90-year-old man presented with painless, fresh rectal bleeding, but was otherwise asymptomatic. Examination was normal except for the fresh blood on rectal examination. He had undergone colonoscopy for a previous episode of bleeding, which had shown only diverticulosis and no treatment had been required. His colonoscopy on admission showed diverticulosis without active bleeding. After a recurrence of his bleeding, he underwent small-intestinal enteroscopy, which was negative, but a further colonoscopy revealed two bleeding sigmoid diverticula and five endoclips were placed ([Fig. 1]). This initially secured hemostasis but he had another recurrence 2 days later. This time he underwent a 99 mTc-labeled red cell scan, which was also negative.
Complement Dysregulation and Disease: Insights from Contemporary Genetics
Authors: M. Kathryn Liszewski, Anuja Java, Elizabeth C. Schramm, John P. Atkinson
Journal: Annual Review of Pathology Mechanisms of Disease (2016)

The vertebrate complement system consists of sequentially interacting proteins that provide for a rapid and powerful host defense. Nearly 60 proteins comprise three activation pathways (classical, alternative, and lectin) and a terminal cytolytic pathway common to all. Attesting to its potency, nearly half of the system's components are engaged in its regulation. An emerging theme over the past decade is that variations in these inhibitors predispose to two scourges of modern humans. One, occurring most often in childhood, is a rare but deadly thrombomicroangiopathy called atypical hemolytic uremic syndrome. The other, age-related macular degeneration, is the most common form of blindness in the elderly. Their seemingly unrelated clinical presentations and pathologies share the common theme of overactivity of the complement system's alternative pathway. This review summarizes insights gained from contemporary genetics for understanding how dysregulation of this powerful innate immune system leads to these human diseases.
PTPS-15ATRX LOSS PROMOTES TUMOR GROWTH AND IMPAIRS NON-HOMOLOGOUS END JOINING DNA REPAIR IN GLIOMA
Authors: Carl Koschmann, Alexandra Calinescu, Felipe Nunez, Alan Mckay, Janet Fazal Salom, Daniel Thomas, Lakshman Mulpuri, Neha Kamran, Flor Mendez, Marta Dzaman, Jonathon Krasinkiewicz, Rosemary Lemons, Lili Zhao, Henry Appelman, David Ferguson, Vera Gorbunova, Alan Meeker, Chris Jones, Pedro R. Lowenstein, Maria G. Castro
Journal: Neuro-Oncology (2015)

Recent work in human glioblastoma (GBM) has documented recurrent mutations in the histone chaperone protein ATRX. We developed an animal model of ATRX-deficient GBM and showed that loss of ATRX reduces median survival and increases genetic instability. Further, analysis of genome-wide data for human gliomas showed that ATRX mutation is associated with increased mutation rate at the single-nucleotide variant (SNV) level. In mouse tumors, ATRX deficiency impairs nonhomologous end joining and increases sensitivity to DNA-damaging agents that induce double-stranded DNA breaks. We propose that ATRX loss results in a genetically unstable tumor, which is more aggressive when left untreated but is more responsive to double-stranded DNA-damaging agents, resulting in improved overall survival.
PTU-317 Is it worth offering ct colonography (ctc) in patients considered unfit for colonoscopy in a nurse (ssp) pre-assessment clinic within the bowel cancer screening programme?
Authors: N Taggart, W Hymer, M Mbuyongha, H Mark, G Fitzgerald, S Sarkar
Journal: Gut (2015)

<h3>Introduction</h3> Whilst colonoscopy is the only test offered within the BCSP after a positive faecal occult blood (FOB) result, there is often a dilemma whether to offer an alternative test in borderline cases especially now the CTC can be performed without administering full bowel prep. The aim of this study was to review CTC offered as an alternative test following SSP clinic within the Liverpool and Wirral BCSP programme to determine the outcome of patients deemed unfit for colonoscopy. <h3>Method</h3> Datasets and notes of all patients that were deemed as high risk for colonoscopy following SSP assessment that underwent a CTC on the advice of a BCSP colonoscopist were audited between May 2014 and Jan 2015. <h3>Results</h3> Of the 481 patients assessed, 13 underwent CTC (2.7%). The reasons for requesting a CTC were listed as: anticoagulant/anti-platelet therapy in conjunction with permanent pace maker (PPM), implantable cardioverter defibrillator (ICD), CA stents, severe valvular heart disease (n = 6), unstable angina and chronic obstructive pulmonary disease COPD (n = 5), ulcer on abdominal aorta (n = 1) and previous failed colonoscopy (n = 1). MH comments – I would use words rather than abbreviations for PPM, ICD, CA and COPD. The results of the CTC were; normal in 5, minor extra-colonic findings in 3, polyps in 4 and likely colorectal malignancy in 1, meaning that 38% of patients that underwent a CTC had a significant colonic abnormality. Eight patients (62%) were discharged back to the screening programme. The patient with likely colorectal malignancy was referred to MDT and 4 with significant polyps underwent further investigation. Two had flexible sigmoidoscopy with just enema prep, 1 with polypectomy and the other had a polyloop applied to the polyp stalk without polypectomy whilst they continued on Ticagrelor. Another underwent a full colonoscopy with polypectomy. The final patient with a possible small polyp opted for a repeat CTC 6 months after MDT and patient discussion. There were no complications following the 3 endoscopic procedures. <h3>Conclusion</h3> Only a very small percentage went onto have a CTC following SSP clinic. The yield of the CTC was significant. A negative result offered reassurance with a Faecal Occult Blood Test in 2 years. Meanwhile, a positive result tipped the risk to benefit ratio to an ultimately good outcome in these patients as less extensive procedures such as a sigmoidoscopy without oral bowel prep, alternatives to polypectomy or a follow up CTC could be offered. <h3>Disclosure of interest</h3> None Declared.
An Investigation of the Therapeutic Properties of Penicillin. A Report to the Medical Research Council.
Authors: J. N. Barron, R. V. Christie, D. B. Fraser, L. P. Garrod, O. T. Mansfield, H. V. Morgan, R. Mowlem, I. M. Robertson, A. C. Roxburgh, I. A. Roxburgh
Journal: BMJ (1944)
PTU-126 Stromal targeting with phosphodiesterase type 5 inhibitors in oesophageal adenocarcinoma
Authors: A Hayden, A Cowie, E Garcia, S Thirdborough, G Thomas, T Underwood
Journal: Gut (2015)

<h3>Introduction</h3> The UK has the highest age-standardised incidence of oesophageal adenocarcinoma (EAC) worldwide. Deaths from EAC have risen by 50% since the 1970’s and 10-year survival is 1 in 10. An activated stroma (defined by α-SMA positive, Cancer Associated Fibroblasts (CAF)) is associated with poor prognosis across tumour types. We have shown the presence of CAF to be more predictive of survival in EAC than traditional pathological markers.<sup>1</sup>Stromal targeting is a novel area in cancer treatment, no currently licensed drugs are effective in targeting CAF. We describe the repurposing of Phosphodiesterase Type 5 inhibitors (PDE5i) for use in the treatment of EAC. <h3>Method</h3> The effect of PDE5i on EAC CAF was studied using small molecule inhibitors and siRNA knock down in primary cell culture and functional assays; collagen gel contraction, Transwell® invasion and 3D organotypic culture. Weighted correlation gene network analysis (WCGNA) was carried out on publically available gene microarray. <h3>Results</h3> PDE5 expression was upregulated in CAF extracted from EAC patients, compared to matched normal fibroblasts (n = 3). PDE5i significantly decreased the expression of α-SMA by CAF. Functional effects were investigated and a significant decrease in collagen-1 gel contraction (p = 0.012) was observed. Cancer cell migration (p &lt; 0.001) and invasion (p &lt; 0.001) in response to CAF was significantly reduced by PDE5i treatment. siRNA knock down of PDE5 confirmed the effect was PDE5 mediated. WCGNA analysis reveals PDE5 expression correlates with extracellular matrix (ECM) organisation genes (including α-SMA) in EAC. Gene ontology and pathway analysis demonstrate these genes are asscoiated with muscle contraction. <h3>Conclusion</h3> Stromal targeting by CAF inactivation is a new potential treatment for hard to treat solid organ malignancies. We have compelling evidence that PDE5i treatment of EAC CAF significantly decreases; α-SMA expression, contractility and the ability to promote cancer cell invasion. Recent evidence supports the role of CAFs in tumourigenesis and immune modulation,<sup>2,3</sup>PDE5 inhibition of the CAF phenotpye offers the possibility of increased drug deliver (chemo/immunotherapy) and host immune cell infiltration, decreased local and distant cancer growth and invasion. The time is right for the first human trial of PDE5i as an anti-cancer therapy. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Underwood <i>et al</i>. Cancer-associated fibroblasts predict poor outcome and promote periostin-dependent invasion in oesophageal adenocarcinoma. J Pathol. 2015 Han <i>et al</i>. Molecular mechanism underlying the tumor-promoting functions of carcinoma-associated fibroblasts. Tumour Biol. 2015 Fearon, <i>et al</i>. The carcinoma-associated fibroblast expressing fibroblast activation protein and escape from immune surveillance. <i>Cancer Immunol Res</i>. 2014
OC-053 Results of the rolcol study: a randomised controlled trial of right versus left starting position in colonoscopy
Authors: A McGrath, C Stoddart, N Vergis, JM Hoare
Journal: Gut (2015)

<h3>Introduction</h3> Insertion in colonoscopy is technically challenging. Conventionally, colonoscopy begins with patients positioned in the left lateral position (LLP). However, few published studies have explored alternatives and there is consequently little evidence to support LLP. We sought to compare right-lateral (RLP) with LLP to determine which starting position ultimately results in quicker procedures and greatest patient comfort. <h3>Method</h3> 167 patients undergoing scheduled colonoscopy were recruited from two London endoscopy units. Subjects were first stratified by age, gender, BMI and experience of endoscopist. Next, patients were randomised to begin colonoscopy in either the LLP or the RLP 1:1 using random permuted blocks. Primary outcome measure was insertion time to caecum and secondary outcome measures included patient comfort measured by visual analogue scale (VAS) and volume of intravenous sedation used. Subsequently, multiple linear regression with backward elimination was used to create a model that identified independent factors that determine insertion time to caecum (SPSS v22). <h3>Results</h3> The profiles of age, gender, BMI and experience of endoscopist were similar between the two groups (Table 1). Median time to reach the caecum was markedly reduced by RLP compared to LLP (498 vs 698 s; <i>P </i>&lt; 0.01) (Figure 1). Women and those who had previously undergone abdominal surgery gained the greatest benefit from right-sided positioning (women RLP vs LLP: 485 vs 782; .05 and abdominal surgery RLP vs LLP: 481 vs 797s; 0.01). Moreover, patients found RLP more comfortable than LLP (2 vs 3 VAS; .02). There were no differences in the volumes of sedation (mean midazolam RLP vs LLP: 1.8 vs 1.7 mg; <i>P</i>= ns) or analgesia (mean fentanyl RLP vs LLP: 24.7 vs 24.0 μg; <i>P</i>= ns) used for either group. No complications were recorded in either group. Multiple linear regression confirmed starting position in colonoscopy as an independent factor affecting time to reach the caecum (<i>P = </i>0.007), along with experience of endoscopist (<i>P </i>&lt; 0.001) and gender (.048). <h3>Conclusion</h3> Starting colonoscopy with patients lying on the right rather than the left-lateral position reduced the median insertion time to caecum by over 3 min. Moreover, patients found right-sided positioning more comfortable than left-sided positioning. It appears that technically challenging groups, such as women and patients who have previously undergone abdominal surgery, gain the greatest benefit from RLP. Future work should examine the benefits of right-sided positioning at a broader range of endoscopy centres. <h3>Disclosure of interest</h3> None Declared.
Questioning Nicotine Replacement Therapy Without Behavioral Support—Reply
Authors: John A. Cunningham
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Dietary Fat Intake and Survival With Breast Cancer
Authors: David I. Gregorio, James R. Marshall
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Dietary Fat Intake and Survival With Breast Cancer Get access David I. Gregorio, David I. Gregorio Department of Social and Preventive Medicine State University of New York at Buffalo Buffalo, New York 14214 Search for other works by this author on: Oxford Academic PubMed Google Scholar James R. Marshall James R. Marshall Department of Social and Preventive Medicine State University of New York at Buffalo Buffalo, New York 14214 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 77, Issue 4, October 1986, Page 990, https://doi.org/10.1093/jnci/77.4.990 Published: 01 October 1986
The effects of bronchodilators on regional lung sound distribution in patients with COPD
Authors: Masamichi Mineshita, Shin Matsuoka, Teruomi Miyazawa
Journal: European Respiratory Journal (2013)

Background: Bronchodilators have been reported to influence regional lung ventilation in patients with COPD, which may change regional lung sound distribution. Vibration response imaging (VRI) is a lung imaging system for the assessment of breath sounds.

Objective: To evaluate the effects of a short-actingβ2-agonist (SABA) on pulmonary functions and the regional distribution of lung sounds in COPD patients.

Methods: A double-blind crossover trial was performed to compare the treatment of COPD patients with a SABA (20 µg of inhaled procaterol) versus a placebo. The percentage of regional lung sound energy (quantitative lung data [QLD]) was evaluated with VRI. VRI, spirometry and impulse oscillometry (IOS) were performed immediately before and 30 minutes after SABA administration.

Results: Ten male patients (69.6±14.2 years of age, percentage predicted FEV1: 43.8±16.9%) were evaluated. The use of a SABA produced significant functional improvements in the spirometric and IOS measurements. Among the homogeneous emphysema patients (n=7), the upper-lung QLD decreased (24.2±5.8% to 18.8±6.1%, p<0.05) and the lower-lung QLD increased (37.9±12.7% to 46.1±14.3%, p<0.05) following SABA inhalation. However, the significant redistribution of the regional lung QLD to the lower lung field was not observed in two of the three inhomogeneous emphysema patients.

Conclusion: The additional use of a SABA by COPD patients improved their pulmonary function, which was accompanied by changes in regional lung air flow. The distribution of the emphysematous lesion and the bronchial reactivity to SABA appeared to affect the redistribution of the lung sounds following bronchodilator administration.