tbuckley/cabot-search huggingface dataset:
Effect of fundholding on waiting times: database study
Authors: B. Dowling
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objectives:</b> To determine whether fundholding patients have shorter waiting times for surgery than non-fundholding patients and to establish if any such differences resulted from practices attaining fundholding status. <b>Design:</b> Comparison of waiting times of fundholding and non-fundholding patients for elective surgery covered by the fundholding scheme at four providers over four years. Comparison of the waiting times for patients of practices in their last year outside and first year inside the fundholding scheme with those for patients of practices remaining non-fundholding. <b>Setting:</b> West Sussex. <b>Subjects:</b> Over 57 000 patients on the elective waiting list who had operations purchased by a health authority or fundholding practice during 1992-6. Patients with booked or planned elective admissions were excluded. <b>Main outcome measures:</b> Waiting times for patients of fundholding and non-fundholding patients. <b>Results:</b> Patients of fundholding practices had significantly shorter waiting times than those of non-fundholders for all four providers and over all four years. Waiting times for patients did not fall until the year that the practices joined the fundholding scheme. <b>Conclusions:</b> Fundholding shortens waiting times. This may be because purchasing of elective surgery is best done at a practice level or because fundholding practices are funded overgenerously. <h3>Key messages</h3> Debate on the creation of a two tier system as a result of general practice fundholding is based largely on anecdotal evidence Patients of fundholding practices on the elective waiting list at four NHS providers in West Sussex over four years had significantly shorter waiting times for the elective surgery covered by the fundholding scheme than did non-fundholding patients Waiting times for patients of practices in the year before fundholding did not differ from those of patients of other non-fundholders The shorter waiting times of fundholding patients can be attributed to the participation of their practice in the fundholding scheme
EBV-associated T/NK–cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases
Authors: Hiroshi Kimura, Yoshinori Ito, Shinji Kawabe, Kensei Gotoh, Yoshiyuki Takahashi, Seiji Kojima, Tomoki Naoe, Shinichi Esaki, Atsushi Kikuta, Akihisa Sawada, Keisei Kawa, Koichi Ohshima, Shigeo Nakamura
Journal: Blood (2011)
L-type calcium channel targeting and local signalling in cardiac myocytes
Authors: Robin M. Shaw, Henry M. Colecraft
Journal: Cardiovascular Research (2013)

In the heart, Ca2+ influx via CaV1.2 L-type calcium channels (LTCCs) is a multi-functional signal that triggers muscle contraction, controls action potential duration, and regulates gene expression. The use of LTCC Ca2+ as a multi-dimensional signalling molecule in the heart is complicated by several aspects of cardiac physiology. Cytosolic Ca2+ continuously cycles between ∼100 nM and ∼1 μM with each heartbeat due to Ca2+ linked signalling from LTCCs to ryanodine receptors. This rapid cycling raises the question as to how cardiac myocytes distinguish the Ca2+ fluxes originating through L-type channels that are dedicated to contraction from Ca2+ fluxes originating from other L-type channels that are used for non-contraction-related signalling. In general, disparate Ca2+ sources in cardiac myocytes such as current through differently localized LTCCs as well as from IP3 receptors can signal selectively to Ca2+-dependent effectors in local microdomains that can be impervious to the cytoplasmic Ca2+ transients that drive contraction. A particular challenge for diversified signalling via cardiac LTCCs is that they are voltage-gated and, therefore, open and presumably flood their microdomains with Ca2+ with each action potential. Thus spatial localization of Cav1.2 channels to different types of microdomains of the ventricular cardiomyocyte membrane as well as the existence of particular macromolecular complexes in each Cav1.2 microdomain are important to effect different types of Cav1.2 signalling. In this review we examine aspects of Cav1.2 structure, targeting and signalling in two specialized membrane microdomains—transverse tubules and caveolae.
TCT-807 Multi-Slice Computed Tomography Procedural Planning For Transcatheter Mitral Annuloplasty
Authors: Jovana Pavicevic, Andrea Guidotti, Tal Sheps, Maximilian Emmert, Etem Caliskan, Oliver Gaemperli, Fabian Nietlispach
Journal: Journal of the American College of Cardiology (2014)
F-18 FDG PET Findings in a Port Site Recurrence After Laparoscopic Radical Nephrectomy in a Patient With Renal Cell Carcinoma
Authors: Gaurav Malhotra, Narendra Nair, Amit Abhyankar, Sushama Awasare, Surendra H. Moghe
Journal: Clinical Nuclear Medicine (2008)

Laparoscopic radical nephrectomy is considered as an alternative to open surgery for localized renal cell carcinoma (RCC). However following this procedure, metastases to the port site have been infrequently reported. We report the FDG PET scan findings in a case of port site recurrence after laparoscopic radical nephrectomy. A 56-year-old man presented with painless hematuria of 3 months duration. He was evaluated and found to have a large heterogeneously enhancing soft tissue density mass (8 × 6.9 × 5.9 cm) in the upper and medial segments of the left kidney on CT. In view of features suggestive of neoplastic etiology the patient underwent laparoscopic left radical nephrectomy. Histopothalogy of the primary was high-grade urothelial carcinoma arising from the renal pelvis and the disease was stage II (T2 N0 M0). After surgery the patient received external beam radiotherapy (EBRT) to the left renal bed to a total of 50 Gy in 25 fractions in 36 days. Thereafter the patient developed a 2 × 2 cm nodule in the anterior abdominal wall at the site of laparoscopic port. Wide excision of the same was done and the patient was referred for FDG PET scan to evaluate disease status. Histopathology of the abdominal wall nodule revealed metastatic deposits of the carcinoma cells in the soft tissue. F-18 FDG PET scan done after 370 MBq (10 mCi) of tracer injection revealed hypermetabolic foci in the liver and anterior abdominal wall suggestive of active disease. F-18 FDG PET seems to be a valuable tool to assess port site recurrence and to restage disease even after so called "curative" resection of the tumor. The rarity of port site recurrence with additional information of disease status provided by FDG-PET merits the use of this modality in post-treatment evaluation of these patients.
Substaging cancers gives treatment flexibility
Authors: William A. Check
Journal: JAMA (1979)

One of the most puzzling questions in cancer treatment is why patients with tumors of apparently similar type and stage don't all respond to the same treatment. In two separate studies investigators have now discovered (1) clues in biopsy specimens that may predict which women with stage I breast cancer are most likely to have recurrences after surgery and (2) which patients with invasive bladder cancer are most likely to benefit from preoperative radiation therapy. If the findings hold up, they could prove valuable in helping physicians decide which patients need the most aggressive treatment and in the design of therapeutic trials to discover more effective therapies. Analysis of patients with breast cancer was done by Thomas Nealon, MD, director of surgery at Saint Vincent's Hospital in New York City and professor of surgery at the New York University School of Medicine, and John Gilloolley, MD, director of pathology at
Limited forward trafficking of connexin 43 reduces cell-cell coupling in stressed human and mouse myocardium
Authors: James W. Smyth, Ting-Ting Hong, Danchen Gao, Jacob M. Vogan, Brian C. Jensen, Tina S. Fong, Paul C. Simpson, Didier Y.R. Stainier, Neil C. Chi, Robin M. Shaw
Journal: Journal of Clinical Investigation (2010)

Gap junctions form electrical conduits between adjacent myocardial cells, permitting rapid spatial passage of the excitation current essential to each heartbeat. Arrhythmogenic decreases in gap junction coupling are a characteristic of stressed, failing, and aging myocardium, but the mechanisms of decreased coupling are poorly understood. We previously found that microtubules bearing gap junction hemichannels (connexons) can deliver their cargo directly to adherens junctions. The specificity of this delivery requires the microtubule plus-end tracking protein EB1. We performed this study to investigate the hypothesis that the oxidative stress that accompanies acute and chronic ischemic disease perturbs connexon forward trafficking. We found that EB1 was displaced in ischemic human hearts, stressed mouse hearts, and isolated cells subjected to oxidative stress. As a result, we observed limited microtubule interaction with adherens junctions at intercalated discs and reduced connexon delivery and gap junction coupling. A point mutation within the tubulin-binding domain of EB1 reproduced EB1 displacement and diminished connexon delivery, confirming that EB1 displacement can limit gap junction coupling. In zebrafish hearts, oxidative stress also reduced the membrane localization of connexin and slowed the spatial spread of excitation. We anticipate that protecting the microtubule-based forward delivery apparatus of connexons could improve cell-cell coupling and reduce ischemia-related cardiac arrhythmias.
Evaluation of staining methods for resin embedded cutaneous tissue sections of mycosis fungoides
Authors: A.C. CHU, N. SMITH, D.M. MACDONALD
Journal: British Journal of Dermatology (1980)

Biopsies from lesional skin of patients with histologically confirmed mycosis fungoides were embedded in resin and semi-thin ( I micrometer) sections were submitted to a variety of staining procedures, including Toluidine blue, Richardson's Huber, Giemsa, Paragon and Tribasic stains. The stained sections were examined with the light microscope and the quality of cellular morphological detail afforded by the different stains was assessed. The Toluidine blue, Richardson's and Paragon stains were found to be technically easy to perform and gave the best representation of nuclear and cytoplasmic detail Of these, the authors favoured Richardson's stain. The technique of processing the tissue, and staining a mounting procedures are detailed.
Long-term canine exposure studies with ambient air pollutants
Authors: J Heyder, S Takenaka
Journal: European Respiratory Journal (1996)

Dogs are often the species of choice as an experimental model for the study of pulmonary responses to long-term exposure to air pollutants in chambers simulating environmental or occupational exposure in man. Their lungs bear a reasonable resemblance to human lungs, they are large enough to allow serial measurements of pulmonary responses, and they live long enough to ensure that findings are not confounded by aging. Several long-term canine exposure studies with ambient air pollutants have been performed since 1957: seven studies with gaseous and particulate sulphur (IV); three studies with nitrogen oxides; three studies with ozone; two studies with acidic particles; three studies with mixtures of sulphurous pollutants that might have resembled the 1952 London smog; and one study in which raw and ultra violet (UV)-irradiated motor vehicle exhaust and sulphurous pollutants were used. The findings support the hypothesis that long-term exposure to air pollutants at ambient levels might cause bronchitic lesions (sulphur oxide), emphysematous lesions (nitrogen dioxide) or fibrotic lesions (ozone). None of the studies showed an indication of synergistic effects. To improve our understanding of pulmonary responses initiated by the inhalation of pollutants over long periods of time, new concepts are needed. Investigators should consider studies with canine models of cardiopulmonary diseases, the application of novel immunological and molecular biology techniques, the phenomena of tolerance and adaptation to inhaled air pollution, and exposure atmospheres with increasing complexity, including fine and ultrafine particles.
Suppression of recurrent non-genital herpes simplex infection by prophylactic oral acyclovir
Authors: R. Meyrick Thomas, H.J. Doddf, Jane M. Yeo, J.D.T. Kirby
Journal: British Journal of Dermatology (1985)

Journal Article Suppression of recurrent non‐genital herpes simplex infection by prophylactic oral acyclovir Get access R. Meyrick Thomas, R. Meyrick Thomas Department of Dermatology, St Bartholomew's Hospital, London EC1 Search for other works by this author on: Oxford Academic Google Scholar H.J. Doddf, H.J. Doddf Department of Dermatology, Royal Free Hospital, London NW3 Search for other works by this author on: Oxford Academic Google Scholar Jane M. Yeo, Jane M. Yeo Clinical and Applied Research Division, Wellcome Research Laboratories, Beckenham Search for other works by this author on: Oxford Academic Google Scholar J.D.T. Kirby J.D.T. Kirby Department of Dermatology, St Bartholomew's Hospital, London EC1 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue s29, 1 July 1985, Pages 21–22, https://doi.org/10.1111/j.1365-2133.1985.tb12976.x Published: 01 July 1985
Senior Casulaty Officers
Authors: E. P. Abson, D. B. Caro
Journal: BMJ (1965)

Charter will do anything to help us with this impossible work load."With the present net loss of principals running at a rate of over 200 in five months, the general practitioner is faced with an in- evitable increase in this load which seems likely to be a geometric progression.On the other hand, as a result of these losses the Pool will be £600,000 the poorer.The pro- fession must decide whether the Minister's suggestions for a publicity campaign are likely to be more effective in reducing un- necessary demand than a discretionary charge
Evidence-Based Evaluation for Allergies to Avoid Inappropriate Testing, Diagnosis, and Treatment
Authors: David P. Huston, Linda S. Cox
Journal: JAMA Internal Medicine (2014)

In the midst of an examination room cluttered with crayons, coloring books, and toys intended to pacify or bribe children during allergy skin testing, an anxious mother attended to her active 4-year-old son. A glance at the appointment book before walking into the room indicated that the reason for this new patient visit was “food allergies.” The interview began with the usual “why are you here” question. The mother’s response: she wanted to know what foods her son was really allergic to and were causing his hyperactivity (attention-deficit/ hyperactivity disorder [ADHD]). An Internet search had directed her to various blogs and support groups encouraging her to have her son tested for allergies. She found a physician who promised that one easy blood test could determine the best elimination diet to treat ADHD. The test results showed that he was allergic to “many things,” most of which he had eaten on a regular basis without any apparent reaction. However, she heeded the advice of her Internet ADHD “expert” and began to eliminate the foods from his diet. During the office visit, she said that she saw no difference in his behavior on the various elimination diets. In fact, she thought that his behavior had gotten worse because he could not eat his favorite foods. Yet she was worried that reintroducing the foods might be harmful.
Infectious Endocarditis as a Result of Contamination during Cardiac Catheterization
Authors: Paul Winchell
Journal: New England Journal of Medicine (1953)

A SEARCH of the medical literature through 19S0 does not reveal any reported cases of bacterial endocarditis following cardiac catheterization. The following case seems to represent an example of temporal and probably causal relation.Case ReportA 44-year-old woman was first admitted to the hospital on November 28, 1951. There was a well substantiated history of rheumatic fever at the age of 10, but there were no symptoms of any kind until 1943, when she noted the onset of dyspnea. A diagnosis of mitral stenosis was made, and digitalis therapy was started in 1946. In November, 1950, she apparently experienced . . .
The neurotensin gene is a downstream target for Ras activation.
Authors: B M Evers, Z Zhou, P Celano, J Li
Journal: Journal of Clinical Investigation (1995)

Ras regulates novel patterns of gene expression and the differentiation of various eukaryotic cell types. Stable transfection of Ha-ras into the human colon cancer line CaCo2 results in the morphologic differentiation to a small bowel phenotype. The purpose of our study was to determine whether the Ras regulatory pathway plays a role in the expression of the neurotensin gene (NT/N), a terminally differentiated endocrine product specifically localized in the gastrointestinal tract to the adult small bowel. We found that CaCo2-ras cells, but not parental CaCo2, express high levels of the human NT/N gene and, moreover, that this increase in gene expression is regulated at the level of transcription. Transfection experiments using NT/N-CAT mutation constructs identify the proximal 200 bp of NT/N flanking sequence as sufficient for maximal Ras-mediated NT/N reporter gene induction. Furthermore, a proximal AP-1/CRE motif is crucial for this Ras-mediated NT/N activation. Wild-type Ha-ras induces NT/N gene expression, albeit at lower levels than activated Ras; a dominant-negative Raf blocks this NT/N induction, suggesting that Raf lies down-stream of Ras in this pathway. In addition, postconfluent cultures of CaCo2 cells, which are differentiated to a small bowel phenotype, express the NT/N gene by 6 d after reaching confluency; this increase of NT/N expression is associated with concomitant increases of cellular p21ras protein. We conclude that Ras (both wild-type and activated) enhances expression of the NT/N gene in the gut-derived CaCo2 cell line, suggesting an important role for the Ras signaling pathway in NT/N gene transcription. Our results underscore the possibility that tissue-specific genes (such as NT/N) expressed in distinct subpopulations of the gut may be subject to Ras regulation. Finally, we speculate that the NT/N gene and the CaCo2 and CaCo2-ras cell systems will provide unique models to further define the cellular mechanisms leading to mammalian intestinal differentiation.
Abstract 1078: Cancer-associated fibroblasts promote endometrial cancer cell proliferation in vitro and in vivo
Authors: Ivy Chung, Kavita S. Subramaniam, Seng Tian Tham, Zahurin Mohamed, Noor Azmi Mat Adenan, Yin Ling Woo
Journal: Cancer Research (2014)

Abstract Cancer-associated fibroblasts (CAFs) recently demonstrated tumor-promoting roles in various cancer types, yet their implication in endometrial cancer (EC) has not been fully explored. We isolated fibroblasts (CAFs) and its epithelial counterpart from human EC tissues using CD90- and CD326-antibodies conjugated magnetic beads, respectively. We collected CAFs secretion by concentrating spent supernatants from cells growing in media containing 2% fetal bovine serum. Both human EC cell lines and primary EC epithelial cells showed increased cell proliferation in a dose-dependent manner, following treatment with CAFs secretion. This was in contrast to the growth inhibitory effects shown with secretions from normal endometrial fibroblasts. EC cells also demonstrated increased cell motility and invasiveness in response to CAFs secretion. Using cytokine array and ELISA, we further identified several cytokines which were overexpressed in CAFs compared to normal endometrial fibroblasts: macrophage chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), growth regulated oncogene (GRO), regulated on activation, normal T cell expressed and secreted (RANTES) and vascular endothelial growth factor (VEGF). These cytokines may activate MAPK/Erk and/or PI3K/Akt pathways to promote EC cell proliferation, as shown by immunoblotting and ELISA. Indeed, CAFs-mediated EC proliferation was suppressed independently by specific inhibitors for PI3K/Akt (LY294002) and MAPK/Erk (U0126). To determine if CAFs promote EC tumor proliferation in vivo, we inoculated fluorescently labeled-epithelial cell and CAFs subcutaneously at the flank of nude mice in the ratio of 1:2 and 1:4. Tumor sizes were measured twice a week using calipers and monitored weekly using in vivo imaging. Inoculation of CAFs and normal fibroblasts alone did not induce any tumor growth; however, co-injection of EC with CAFs (1:4) showed approximately 3 times higher growth rate when compared to EC alone. More interestingly, there was no sign of tumor growth in mice inoculated with combination of EC and normal fibroblasts (1:4) at the end of experiment. Taken together, our data suggests that CAFs exert tumor-promoting effects both in vitro and in vivo partly via specific cytokines-mediated activation of MAPK/Erk and PI3K/Akt pathways. Delineating the roles of CAFs in EC tumor microenvironment may provide potential therapeutic targets for the treatment of EC. Citation Format: Ivy Chung, Kavita S. Subramaniam, Seng Tian Tham, Zahurin Mohamed, Noor Azmi Mat Adenan, Yin Ling Woo. Cancer-associated fibroblasts promote endometrial cancer cell proliferation in vitro and in vivo. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1078. doi:10.1158/1538-7445.AM2014-1078
Small Interfering Double-Stranded RNAs as Therapeutic Molecules to Restore Chemosensitivity to Thymidylate Synthase Inhibitor Compounds
Authors: John C. Schmitz, Tian-min Chen, Edward Chu
Journal: Cancer Research (2004)

Abstract RNA interference is a post-transcriptional mechanism by which double-stranded RNA specifically silence expression of a corresponding gene. Small interfering double-stranded RNA (siRNA) of 21–23 nucleotides can induce the process of RNA interference. Studies from our laboratory have shown that translation of thymidylate synthase (TS) mRNA is controlled by its own protein end-product TS in a negative autoregulatory manner. Disruption of this process gives rise to increased synthesis of TS and leads to the development of cellular drug resistance to TS-targeted compounds. As a strategy to inhibit TS expression at the mRNA level, siRNAs were designed to target nucleotides 1058–1077 on human TS mRNA. Transfection of TS1058 siRNA into human colon cancer RKO cells resulted in a dose-dependent inhibition of TS expression with an IC50 value of 10 pm but had no effect on the expression of α-tubulin or topoisomerase I. Inhibition of TS expression by TS1058 was maximal at 48 h and remained suppressed for up to 5 days. Pretreatment of RKO cells with TS1058 siRNA suppressed TS protein induction following exposure to raltitrexed. In addition, TS1058 restored chemosensitivity of the resistant RKO-HTStet cell line to various TS inhibitor compounds. On treatment with TS1058, IC50 values for raltitrexed, 1843U89, and 5-fluoro-2′-deoxyuridine decreased by ∼15–16-fold. These studies suggest that TS-targeted siRNAs are effective inhibitors of TS expression and may have therapeutic potential by themselves or as chemosensitizers in combination with TS inhibitor compounds.