tbuckley/cabot-search huggingface dataset:
Methylguanine methyltransferase–mediated in vivo selection and chemoprotection of allogeneic stem cells in a large-animal model
Authors: Tobias Neff, Peter A. Horn, Laura J. Peterson, Bobbie M. Thomasson, Jesse Thompson, David A. Williams, Manfred Schmidt, George E. Georges, Christof von Kalle, Hans-Peter Kiem
Journal: Journal of Clinical Investigation (2003)

Clinical application of gene therapy for genetic and malignant diseases has been limited by inefficient stem cell gene transfer. Here we studied in a clinically relevant canine model whether genetic chemoprotection mediated by a mutant of the DNA-repair enzyme methylguanine methyltransferase could circumvent this limitation. We hypothesized that genetic chemoprotection might also be used to enhance allogeneic stem cell transplantation, and thus we evaluated methylguanine methyltransferase–mediated chemoprotection in an allogeneic setting. We demonstrate that gene-modified allogeneic canine CD34+ cells can engraft even after low-dose total body irradiation conditioning. We also show that cytotoxic drug treatment produced a significant and sustained multilineage increase in gene-modified repopulating cells. Marking in granulocytes rose to levels of up to 98%, the highest in vivo marking reported to date to our knowledge in any large-animal or human study. Increases in transgene-expressing cells after in vivo selection provided protection from chemotherapy-induced myelosuppression, and proviral integration site analysis demonstrated the protection of multiple repopulating clones. Drug treatment also resulted in an increase in donor chimerism. These data demonstrate that durable, therapeutically relevant in vivo selection and chemoprotection of gene-modified cells can be achieved in a large-animal model and suggest that chemoprotection can also be used to enhance allogeneic stem cell transplantation.
UEGW Congress Report, Copenhagen 2005: Review of Endoscopic Abstracts
Authors: T. Rösch
Journal: Endoscopy (2006)

Assessing the quality of the endoscopic abstracts accepted at the United European Gastroenterology Week (UEGW) meeting is always necessarily subjective and may reflect the progress of endoscopic research as well as peculiarities of the selection committees. Nevertheless, the author’s subjective impression for 2005 was that less original work primarily sent to UEGW was available. In fact, many large studies recently presented were not seen at UEGW - e. g. papers on double-balloon endoscopy and reports on some new colonoscopes. Instead, a few new techniques were sometimes reported without clear-cut results, although the authors told us how happy they were. Let’s hope this will change in the years to come.
Thrombocytopenia associated with legionnaires' disease.
Authors: T M Gasper, P A Farndon, R Davies
Journal: BMJ (1978)

aluminium concentration was ten times higher than normal, while no other blood values were abnormal.Finally, the interruption of oral aluminium intake and the reduction of the aluminium concentration in the dialysis fluid were followed by progressive clinical improvement and cure within one month.It is difficult to determine whether aluminium intoxication is due mainly to digestive absorption after oral intake or to the high con- centration of aluminium in dialysis fluid.Generally the concentration of aluminium in dialysis fluid plays an important part in intoxica- tion,2 though prolonged ingestion of aluminium salts during chronic renal failure may be responsible for causing encephalopathy.The fact that encephalopathy due to aluminium toxicity may be reversed by stopping aluminium administration indicates the importance of performing repeated measurements of blood aluminium concentra- tions in patients undergoing haemodialysis and of controlling the aluminium content in dialysis fluid.When considered with EEG and clinical data these measurements may lead to early diagnosis of aluminium toxicity and reversal of the usually fatal course of dialysis encephalopathy.
Abstract 1603: Primary breast cancer xenografts maintain the molecular profiles of corresponding patients’ tumors and recapitulate a part of stroma microenvironment
Authors: Fabien Reyal, Charlotte Guyader, Charles Decraene, Carlo Lucchesi, Nathalie Auger, Franck Assayag, Ludmilla De Plater, David Gentien, Marie-France Poupon, Paul Cottu, Patricia De Cremoux, Anne Vincent-Salomon, Sergio Roman-Roman, Olivier Delattre, Didier Decaudin, Elisabetta Marangoni
Journal: Cancer Research (2011)

Abstract Identifying new therapeutic agents for breast cancer (BC) treatment requires preclinical models that recapitulate the molecular characteristics of their respective clinical tumors. In this work, we analyzed the genomic and expression profiles of human BC xenografts and their corresponding patient's tumors. Eighteen BC xenografts were obtained by grafting tumor fragments from patients into Swiss nude mice. The molecular characterization of patient's and xenograft's tumors (early and late in vivo passages) was performed by DNA copy number analysis (aCGH) and gene expression analysis using Affymetrix Microarrays. Comparison of genomic profiles of BC xenografts with those of respective patient's tumors, showed a correlation coefficient higher than 0.50 in 14/18 paired tumors. Unsupervised hierarchical clustering analysis showed that 16/18 pairs segregated together further indicating the striking similarity between pairs. At the level of gene expression profile few variations were found between patient's tumor and their respective xenografts, i.e. 371 genes that were differentially expressed in more than 84% of paired tumors and that largely represent human stromal compartment related genes. Furthermore, analysis of gene expression by murine stroma revealed a partial but significant recapitulation of the primitive human stroma. Finally, we found that sequential mouse to mouse tumor passages did not affect neither genomic rearrangements nor gene expression profiles, suggesting a striking genetic stability of these models across the time. In conclusions, this panel of human BC xenografts accurately maintains the genomic and the expression profiles of their corresponding patient's tumors and are stable across sequential in vivo passages. Consequently, these xenografts represent a validated model for preclinical investigation of new therapeutic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1603. doi:10.1158/1538-7445.AM2011-1603
New Guidelines for Coding Physicians' Services — A Step Backward
Authors: A S Brett
Journal: New England Journal of Medicine (1998)

In July 1998, the Health Care Financing Administration (HCFA) intended to implement a revised and more complex set of guidelines specifying how physicians should code and document “evaluation and management” services billed to Medicare. These services include office visits and hospital visits and are distinguished from surgery and other invasive procedures. In 1996, Medicare payments for evaluation and management services totaled about $16 billion, or 40 percent of payments to physicians under the program.1 Before the proposed date of implementation, the new guidelines created considerable turmoil among practicing physicians and were a subject of spirited and sometimes angry commentary in . . .
S105 Endotoxin Specific IgG2 Antibodies Impair Bacterial Killing in Non Cystic Fibrosis Bronchiectasis Patients Colonised with Pseudomonas Aeruginosa
Authors: D Whitters, TJ Wells, IR Henderson, RA Stockley
Journal: Thorax (2012)

<h3>Introduction</h3> We have previously identified patients colonised with <i>Pseudomonas aeruginosa</i> (PA), in whom strains isolated from their sputum cannot be killed by their serum, yet are fully sensitive to healthy control serum (HCS). Addition of inhibitory patient serum to HCS also impaired killing of PA. Fractionation of patient serum identified that IgG was responsible for the inhibition. FACS demonstrated excessive binding of IgG2 from patient serum to autologous strains. Visualisation of lipopolysaccharide (LPS) isolated from bacterial strains by silver staining, showed that strains from patients with inhibitory serum demonstrated detectable O antigen expression – a component of the LPS cell wall of PA. We aimed to confirm this relationship between inhibitory IgG2 and LPS expression by PA. <h3>Methods</h3> Anti-LPS antibodies were removed from inhibitory serum (S4) by binding LPS from PA isolated from patient sputum, to polymyxin-B agarose overnight. Inhibitory serum was then passed over the LPS bound column. Antibodies specific for LPS bound to the column, and the flow through fractions of serum were collected. Bound antibody was subsequently buffer exchanged into PBS. LPS was isolated from a PA strain resistant to patient sera (B4) and attached to a 96 well plate. ELISA was performed by adding dilutions of patient or HCS to the plate followed by anti-human IgG2 conjugated to alkaline phosphotase. Results were derived 30 minutes after addition of developer. <h3>Results</h3> LPS removal of IgG from the patient’s serum restored bacterial killing. Adding the eluted antibody to HCS impaired killing. This confirmed that inhibitory IgG2 is LPS specific. The patients’ serum that blocked bacterial killing had high titres of IgG2 to LPS compared to those from patients with bactericidal serum (fig. 1) <h3>Conclusion</h3> We have established that PA strains deficient in LPS O antigen are generally sensitive to killing by patients’ serum, whilst the presence of O antigen leads to serum resistance mediated by IgG2. <h3>Results</h3> indicate that PA LPS O antigen repeats are central to serum resistance of autologous strains but not normal HCS. Current data indicates that bacterial killing is impaired in subjects colonised with PA expressing O antigen due to overproduction of LPS specific IgG2.
BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgVH unmutated chronic lymphocytic leukemia (CLL) cells
Authors: Anna Guarini, Sabina Chiaretti, Simona Tavolaro, Roberta Maggio, Nadia Peragine, Franca Citarella, Maria Rosaria Ricciardi, Simona Santangelo, Marilisa Marinelli, Maria Stefania De Propris, Monica Messina, Francesca Romana Mauro, Ilaria Del Giudice, Robert Foà
Journal: Blood (2008)
Teenagers and contraception.
Authors: J D Havard
Journal: BMJ (1986)

The position regarding confidentiality had been reasonably clear until the General Medical council (GMC) revised its guidance to doctors about their responsibilities to females under the age of 16.  If a girl was so immature that she could not understand the consequences of sexual intercourse and the nature of any treatment the doctor considered necessary contraceptive examination advice or treatment should not be provided without informing the girls parents.  Whether or not the doctor decided to proceed all that was possible had to be done to persuade the girl to allow her parents to be imformed so that they could provide support for her in difficult and potentially dangerous circumstances.  If the doctor did not proceed nothing in the GMC guidance would justify the doctor informing the parents that girl had consulted him -- and still less passing on information she had given during the consulation.  Well before the National Health Services contraceptive service was introduced in 1975 the GMC had strongly criticized a doctor who had notified the parents of an under-age girl that she had attended a family planning clinic.  The reason for this strict attitude towards confidentiality was the paramount importance of persuading such girls to seek advice from the sources they are most likely to consult -- a doctor -- instead of less responsible and less well informed sources of advice.  The guidance issued by the GMC the BMA and the Department of Health and Social Security emphasized the duty of the doctor to persuade girls under 16 seeking treatment to allow their parents to be informed but all 3 bodies recognized (and this was clearly stated by Lord Fraser in the House of Lords decision in the Gillick case) that if the girl feared that her parents would be informed she would be unlikely to approach a doctor.  Throughout the controversy over the Gillick case the BMA has maintained that free access to the doctor was the best insurance parents could have against their remaining unaware that their daughters were engaged in precocious sexual intercourse and the dangers of what entails.  Mrs. gillicks case rested on 2 beliefs:  that if girls are discouraged from seeking medical advice they will stop engaging in sexual intercourse; and that a doctor who fails to inform the parents is aiding and abetting a criminal offense.  The formed claim is contrary to the experience of doctors who have to deal with such cases and not even the Court of Appeal was able to support the latter.
Genetic susceptibility to non-insulin dependent diabetes
Authors: L Groop, G F Bottazzo
Journal: BMJ (1994)

EDITOR, - Eva Tuomilehto-Wolf and coworkers have presented the interesting hypothesis that genetic susceptibility to non-insulin dependent diabetes mellitus is located in the HLA region. Their conclusions are based on findings in 157 elderly Finnish men (age 70-89), in whom HLA haplotypes associated with insulin dependent diabetes could explain 98% of non-insulin dependent diabetes and 79% of impaired glucose tolerance. This association depended strongly …
Prescribing for surgical patients compared to overall prescribing skills of foundation year 1 doctors: A study by the avoiding prescribing errors (APE) committee
Authors: Sarantos Kaptanis, Louise Congdon, Nick Ward, Luke Arwynck, Charlene McInnes, Dhanesh Solanki, Gideon Kotey, Stella Vig
Journal: International Journal of Surgery (2012)
Severe immune thrombocytopenic purpura relapse after alpha‐interferon in chronic myeloid leukemia, successfully treated with cyclosporine
Authors: Luigi Cavanna, Daniele Vallisa, Raffaella Berte, Elisabetta Buscarini, Fabio Fornari, Michele Di Stasi, Giuseppe Civardi, Luigi Buscarini
Journal: American Journal of Hematology (1994)
8th Georg Rajka International Symposium on Atopic Dermatitis: meeting report
Authors: S.M.C. George, A. Makrygeorgou
Journal: British Journal of Dermatology (2015)

The 8th Georg Rajka International Symposium on Atopic Dermatitis was held in Nottingham in May 2014. The 3-day meeting featured a number of lectures by experts in the field of atopic dermatitis from around the world, as well as several original research presentations and a question and answer session. This paper aims to summarize the main oral presentations from the meeting, but is not meant to be a substitute for reading the conference proceedings and related references.
Clinical Evaluation of Aminocaproic, Acid for Managing Traumatic Hyphema in Children
Authors: Barbara K. Teboul, Jean-Louis Jacob, Magda Barsoum-Homsy, Isabelle Brunette, Line Chevrette, Jean Milot, Jacqueline Orquin, Robert C. Polomeno, Michael G. Quigley
Journal: Ophthalmology (1995)
Malaria prophylaxis: survey of the response of British travellers to prophylactic advice.
Authors: P A Phillips-Howard, M Blaze, M Hurn, D J Bradley
Journal: BMJ (1986)

A cohort study was conducted to determine the compliance of travellers with chemoprophylactic advice given over the telephone by the malaria reference advisory service. Travellers who visited their general practitioner first for advice about malaria prophylaxis were often advised to consult a specialist service themselves. Compliance fell in travellers who were given complicated information and those who received conflicting advice when they contacted other advisory services. After returning to Britain 48% of the travellers reported that they were fully compliant with prophylactic advice; over a third of the travellers studied did not maintain prophylaxis on their return.
RECENT PROGRESS I SURGICL TREATMENT OF MALIGNANT GROWTHS
Authors: JOSEPH C. BLOODGOOD
Journal: JAMA (1910)

The problem assigned to me is strictly a practical one, and if there has been any recent progress in the surgical treatment of malignant growths, it has been due to the fact that a number of surgeons have been critically investigating the accumulated evidence of years of experience in the results of their interventions to eradicate malignant disease. The best results have been obtained only in those cases in which there has been a painstaking study of the pathologic picture, an exact record of the extent of the operation,or other methods of treatment, and of the ultimate results. In my opinion the recent progress has led to a better conception, not only of the pathologic varieties of the different neoplasms, but also of their local growth and tendency to metastasis. Surgeons are beginning to learn that in some instances the extent of the local operation must be increased, while in
Percutaneous Ethanol Injection of the Prostate as Minimally Invasive Treatment for Benign Prostatic Hyperplasia: Preliminary Report
Authors: Gianfranco Savoca, Stefano De Stefani, Ignazio Gattuccio, Daniele Paolinelli, Fulvio Stacul, Emanuele Belgrano
Journal: European Urology (2001)
Treatment of Thyrotoxic Storm with Intravenous Administration of Propranolol
Authors: GOPAL DAS
Journal: Annals of Internal Medicine (1969)

Thyrotoxic storm is a rare but serious complication of thyrotoxicosis. Proper preoperative preparation of the thyrotoxic patient and the therapeutic use of radioactive iodine (131I) have reduced its incidence. Treatment is still unsatisfactory, however, as is evidenced by the mortality figures (20 to 50%). It has been shown recently that most of the cardiovascular and metabolic manifestations of thyrotoxicosis can be controlled effectively by blockade of the beta adrenergic receptors of the body. Intravenous administration of propranolol was immediately effective in the management of thyrotoxic storm in our patient, who did not respond to other modes of therapy.
1014-209 High risk of obstructive sleep apnea in patients with atrial fibrillation
Authors: Apoor S Gami, Sean M Caples, Ravi Kanagala, Elizabeth H Nora, Stephen T Turner, Gary L Schwartz, Narayana S Murali, Joseph F Malouf, Naser M Ammash, Paul A Friedman, Virend K Somers
Journal: Journal of the American College of Cardiology (2004)
Parity and breast cancer: evidence of a dual effect.
Authors: K L Woods, S R Smith, J M Morrison
Journal: BMJ (1980)

Epidemiological studies have shown that early first pregnancy reduces the risk of developing breast cancer, which indicates that initiation of the disease occurs at an early age. Thus the subclinical lesion of breast cancer might already be present in the breast before childbearing begins and the growth of any such focus might be modified by the endocrine changes of pregnancy. To test this hypothesis the relation between parity and age at presentation was studied in 341 unselected patients with breast cancer presenting to a single clinic. The mean age at presentation was 5.2 years lower in parous than nulliparous women (p < 0.001) and fell with increasing parity. It is concluded that reproductive history influences not only the risk of breast cancer but also the latent interval of a proportion of breast carcinomas.Epidemiological studies have shown that early 1st pregnancy reduces risk of developing breast cancer, thus suggesting that initiation of the disease occurs at an early age. Therefore, the subclinical lesion of breast cancer might already be present in the breast before childbearing begins and the growth of any such focus might be modified by the endocrine changes of pregnancy. To test this hypothesis the relation between parity and age at presentation was studied in 341 unselected patients with breast cancer presenting at a single clinic. The mean age at presentation was 5.2 years lower in parous than nulliparous women (P 0.001) and fell with increasing parity. The conclusion is drawn that reproductive history influences not only the risk of breast cancer but also the latent interval of a proportion of breast carcinomas.
The Use of Part I National Board Scores in the Selection of Residents in Ophthalmology and Otolaryngology
Authors: Robert J. McCollister
Journal: JAMA (1988)

A survey of ophthalmology and otolaryngology residency program directors was conducted to determine the extent to which National Board of Medical Examiners (NBME) Part I scores are used in selection of residents in these highly competitive specialty fields. Results from 218 completed questionnaires representing nearly 90% of all US ophthalmology and otolaryngology/head and neck surgery programs were analyzed. More than three fourths indicated that Part I NBME scores were used in selecting residents; more than half of the programs used these scores as a means to determine whom to interview. The direct use of NBME scores in the residency application process is widespread; however, such use of NBME scores is not consistent with the purposes of the National Board. The preeminent role of the faculty in the evaluation of medical students and in the assessment of their clinical competence needs emphasis.
Abstract 2450: Either pan class I PI3K inhibitor or PI3K alpha selective inhibitor sensitizes head and neck squamous cell carcinoma cells to Erlotinib, an EGFR TKI.
Authors: Ming Gao, Yen-Shen Lu, Li-Ping Hsiao, Suz Wen Chen, Ann-Lii Cheng
Journal: Cancer Research (2013)

Abstract The epidermal growth factor receptor (EGFR) is overexpressed in 90% of head and neck squamous cell carcinoma (HNSCC), and is correlated with poor prognosis. EGFR is therefore a potential therapeutic target for HNSCC. However, most HNSCC patients do not respond well to small molecular EGFR inhibitors. One of the possible mechanisms of EGFR TKI resistance is compensatory collateral activation of PI3K/Akt pathway. This study sought to explore whether NVP-BKM120, a selective pan class I PI3 kinase inhibitor, and NVP-BYL719, a novel PI3 kinase alpha selective inhibitor, may reverse the resistance of HNSCC cells toward erlotinib, an EGFR TKI. Cells were treated with the PI3K inhibitors, either BKM120 or BYL719, alone, erlotinib alone, or in combination, and viability was measured at 72 hours with MTT assay. Combination effect was evaluated by median effect analysis. Synergism, indicated by a combination index (CI) value &amp;lt;1, were seen in all five cell lines (SAS, HSC3, UMCC1, CA922 and FaDu) studied. By immunoblotting analysis, combination of Erlotinib and either PI3K inhibitor resulted in dowregulation of p-EGFR and p-AKT expression in SAS cells. When SAS and HSC3 cells were treated with erlotinib in combination with either BKM120 or BYL719, an additional increase in the subG1 population by flow cytometry analysis were observed, indicating an increase of apoptotic cell death. Our data suggest that additional PI3K blockade might be an effective strategy to overcome resistance of HNSCC cells toward EGFR TKIs, and the beneficial effect is similar between pan Class I PI3K inhibitor and PI3K alpha selective inhibitor. (The study was supported by the grant of DOH101-TD-B-111-001). Citation Format: Ming Gao, Yen-Shen Lu, Li-Ping Hsiao, Suz Wen Chen, Ann-Lii Cheng. Either pan class I PI3K inhibitor or PI3K alpha selective inhibitor sensitizes head and neck squamous cell carcinoma cells to Erlotinib, an EGFR TKI. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2450. doi:10.1158/1538-7445.AM2013-2450