tbuckley/cabot-search huggingface dataset:
Sequential Therapy With Fludarabine, High-Dose Cyclophosphamide, and Rituximab in Previously Untreated Patients With Chronic Lymphocytic Leukemia Produces High-Quality Responses: Molecular Remissions Predict for Durable Complete Responses
Authors: Nicole Lamanna, Joseph G. Jurcic, Ariela Noy, Peter Maslak, Alison N. Gencarelli, Katherine S. Panageas, Mark L. Heaney, Renier J. Brentjens, David W. Golde, David A. Scheinberg, Andrew D. Zelenetz, Mark A. Weiss
Journal: Journal of Clinical Oncology (2008)

Modern combination strategies are active in chronic lymphocytic leukemia (CLL) but can have significant myelosuppression and immunosuppression that may require dose attenuation for safety. We explored a sequential treatment strategy to allow safe delivery of active agents at full doses. Previously, we studied sequential therapy with fludarabine followed by cyclophosphamide (F-->C). In that study, cyclophosphamide consolidation improved the frequency of complete response (CR) four-fold. Subsequently, rituximab was added to this regimen (F-->C-->R).Thirty-six previously untreated CLL patients received therapy with fludarabine 25 mg/m(2) on days 1 through 5 every 4 weeks for six cycles, followed by consolidation with cyclophosphamide 3,000 mg/m(2) administered every 3 weeks for three cycles, followed by consolidation with weekly rituximab 375 mg/m(2) for four cycles. Evaluation for minimal residual disease included flow cytometry and a highly sensitive clonotypic polymerase chain reaction (PCR). The median age was 59 years (range, 37 to 71 years), 61% of patients had high-risk disease, and 58% had unmutated IgV(H) genes.There were 32 responses (89%), including 22 CRs (61%). Consolidation with cyclophosphamide improved responses in 13 patients (36%); nine patients (25%) further improved their response with rituximab. Twenty patients (56%) achieved flow cytometric CRs, and 12 patients (33%) achieved a molecular CR (PCR negative). Patients achieving molecular CRs had an excellent prognosis with a plateau in the response duration curve, and 90% remain in clinical CR at 5 years. For the entire group, 5-year survival rate is 71% compared with a rate of 48% with our prior F-->C regimen (P = .10).Sequential therapy with F-->C-->R yields improvement in quality of response, with many patients achieving a PCR-negative state.
Tissue bank expands facilities, efforts
Authors: A. A. Skolnick
Journal: JAMA (1991)

ONCE CALLED the Skin Bank of the University of Texas Medical Branch (UTMB) at Galveston, the UTMB Tissue Bank, as it is now known, collects more than just skin. For the last 2 years, it has been in the business of recycling human bone and has just begun the harvesting of human heart valves and saphenous veins (for coronary artery bypass surgery). The UTMB tissue bank, one of more than 30 nationwide that harvests skin from cadaver donors, began operating 9 years ago. By 1989, it was responsible for procuring approximately 25% of all the donor skin used to treat burn patients in the United States, says Mary G. Hodges, RN, the bank's acting technical director. In addition to procuring skin from 298 donors in 1990, the bank obtained bone from 117 donors, Hodges says. On St Valentine's Day this year, the bank harvested its first heart valve for transplantation.
British Private Medical Practice and the National Health Service
Authors: Philip C. Anderson
Journal: JAMA (1969)

Having survived the naïve strategy of the 1950's to abolish "galloping socialism," American physicians of good mind and moderate politics are ready for a serious study of the problems, and a realistic effort to establish a responsible relationship between ourselves and the conservative majority of the US Congress. The form of private practice will be a principle issue to be studied. The late Samuel Mencher of Pittsburgh understood much about these principle issues, both in the United States and in Great Britain. The books of this quiet man seem unfairly neglected in the continuous clatter from more famous centers. His less-spectacular style often seems more nourishing intellectually, and his comparative technique is scholarly. He shows us the importance of the developments in 1912 which led to the formation of the British National Health Service. We can compare our own history with the British experience as to taxation, poor-laws, welfare, labor
Modulating Angiogenesis
Authors: Branavan Sivakumar, Lorraine E. Harry, Ewa M. Paleolog
Journal: JAMA (2004)

The concept of manipulation of the vascular bed to either increase or decrease the number of blood vessels has attracted considerable interest. This review focuses on angiogenesis as a therapeutic target, particularly in the context of cancer and arthritis, as well as on promoting angiogenesis in cardiovascular disease and the healing of bone fractures. Although once touted almost as a panacea for treatment of tumors, as well as other diseases associated with angiogenesis, such as diabetic retinopathy or rheumatoid arthritis, it is now clear that such enthusiasm was somewhat premature. Similarly, some clinical trials of therapeutic angiogenesis for the management of cardiovascular disease have been disappointing. Nevertheless, this exciting field of research holds promise for more targeted therapies.
Mitral and tricuspid valve closure in congenital heart disease.
Authors: S Milner, R A Meyer, A W Venables, J Korfhagen, S Kaplan
Journal: Circulation (1976)

Echocardiography was used to evaluate mitral and tricuspid valve closure in patients 1 day to 20 years of age. When possible, simultaneous phonocardiograms were obtained. The difference in time between the Q wave of the electrocardiogram and mitral closure and between Q and tricuspid closure was designated the delta value. Four groups of patients were assessed: 1) normals (40), secundum atrial septal defect (ASD) (10), mitral valve prolapse syndrome (Barlow's syndrome) (13), pulmonary hypertension (12), and pulmonic stenosis (6); 2) Ebstein's anomaly (10); 3) transposition of the great vessels (15); 4) right bundle branch block (RBBB) (25). Ten patients with surgically induced right bundle branch block were studied by phonocardiography alone. Group I had values of 50 msec or less (-5 to 50 milliseconds) and served as controls. Ebstein's anomaly showed prolongation of the delta value to 65 msec or greater in eight out of ten patients. Patients with transposition of the great vessels showed a striking difference from the preceding groups in that an average negative delta value was obtained. Twenty-two patients of group 4 (RBBB) had delta values within the normal range. This study has shown that a delta value greater than 65 msec is suggestive of Ebstein's anomaly. In addition, if the delta value is negative, transposition of the great vessels can be suspected.
Melanoma awareness and sun exposure in Leicester
Authors: J. Melia, J. Chamberlain
Journal: British Journal of Dermatology (1996)

Journal Article Melanoma awareness and sun exposure in Leicester Get access J. Melia, J. Melia The Institute of Cancer Research, Royal Cancer Hospital Cancer Screening Evaluation Unit, Block D. 15 Cotswold Road, Sutton, Surrey SM2 5NG, U.K. Search for other works by this author on: Oxford Academic Google Scholar J. Chamberlain J. Chamberlain The Institute of Cancer Research, Royal Cancer Hospital Cancer Screening Evaluation Unit, Block D. 15 Cotswold Road, Sutton, Surrey SM2 5NG, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 134, Issue 2, 1 February 1996, Page 372, https://doi.org/10.1111/j.1365-2133.1996.tb07633.x Published: 01 February 1996
Two lessons about rabies.
Authors: D Parker
Journal: BMJ (1980)

arm into the shoulder but not the praecordium and was accompanied by an episode of vomiting.It was relieved only by diamorphine.Physical examination was normal but later the patient became mildly pyrexial, and serial electrocardiograms and cardiac enzyme assays confirmed an inferior myocardial infarct.The patient made an uncomplicated recovery but has subsequently developed classical symptoms of angina.This patient presented in a busy accident and emergency department and was admitted only because of the severity of her pain.This case emphasises the difficulty of diagnosing atypical cardiac pain.
Hypocalcemia increases and hypercalcemia decreases the steady-state level of parathyroid hormone messenger RNA in the rat.
Authors: M Yamamoto, T Igarashi, M Muramatsu, M Fukagawa, T Motokura, E Ogata
Journal: Journal of Clinical Investigation (1989)

To examine the effects of serum calcium concentrations on PTH biosynthesis, rats were made hyper- (serum total calcium, approximately 3.5 mM) or hypocalcemic (approximately 1.25 mM) and steady-state levels of PTH mRNA in parathyroid cells were measured by the primer extension method using a 32P-labeled synthetic oligomer. PTH mRNA levels increased about twofold in the rats made slightly hypocalcemic by infusion of calcium-free solution and decreased slightly in those made hypercalcemic by CaCl2 infusion (120-150 mumol/h) compared with the levels present in nonfasting control rats. Infusion of calcitonin (0.5 U/h) or EGTA (90 mumol/h) with calcium-free solution increased PTH mRNA levels further (two- to sevenfold) above the levels present in animals infused with calcium-free solution alone. These changes in PTH mRNA levels were observed after 48- but not 24-h infusion, and there was an inverse correlation between PTH mRNA levels and serum calcium concentrations. The results suggest that changes in serum calcium concentrations in the near physiological range regulate the biosynthesis of PTH by affecting steady-state levels of PTH mRNA when hypercalcemia or hypocalcemia continues for a relatively long period.
DIGITALIS IN THE TREATMENT OF CROUPOUS PNEUMONIA.Read in the Section on Practice of Medicine, at the Forty fifth-Annual Meeting of the American Medical Association held at San Francisco, June 5-8, 1894.
Authors: WM. WATT KERR
Journal: JAMA (1894)

It is not my intention to claim that digitalis is a specific in the treatment of croupous pneumonia, nor to insist upon its administration in every case of the disease that presents itself, but simply to state why it may be used and when, in my opinion, it ought to be used. During the last three years there has been considerable discussion, both in Europe and America, upon the use of digitalis in the treatment of pneumonia, and the various writers may be divided into three classes: 1, those who claim that digitalis is a specific in the treatment of pneumonia cutting short or, as they express it, jugulating the disease if given in the first stage; 2, those who have found that the disease is but little if at all influenced by the use of digitalis; 3, those who on theoretical grounds maintain that the administration of digitalis in
Observations on gastric acid output by a three-hour histamine infusion test using maximal doses on patients with duodenal ulcer and in normal controls
Authors: R. M. Hector, J. F. Webb
Journal: Gut (1970)

The results of a series of histamine infusion tests extended over a period of three hours in 100 patients with duodenal ulcer and in 30 normal controls showed that while in the former group acid secretion continued to rise hourly both quantitatively and qualitatively throughout each of the three-hour periods of the tests, this did not occur in the normal controls in whom acid secretion levelled off during the second hour. Assay of 30-minute aspirates in the duodenal ulcer group showed that the 90-120 minute specimen (doubled) gave a close approximation to the values obtained during the third hour and represents maximal acid secretion of the gastric mucosa.
Calcium uptake by intestinal brush border membrane vesicles. Comparison with in vivo calcium transport.
Authors: H P Schedl, H D Wilson
Journal: Journal of Clinical Investigation (1985)

In prior studies, we examined kinetics of steady state in vivo transepithelial calcium transport in rat and hamster. The present studies related calcium uptake by the brush border to in vivo transport. We measured calcium uptake by brush border membrane vesicles from the two species. In the rat, our prior in vivo studies had shown that (a) calcium transport was mediated, (b) no nonmediated component was detectable, and (c) Vmax was 2.5 times greater in proximal than distal small intestine. In brush border membrane vesicles from the rat, Vmax for the saturable component of calcium uptake was again 2.5 times greater in proximal than distal intestine. Contrasting with in vivo studies, a major nonsaturable component was present in vesicles from proximal and distal small intestine. In the hamster, our previous in vivo studies had shown (1) both mediated and nonmediated components of calcium transport, (2) greater nonmediated transport in proximal than distal small intestines, and (3) Vmax for calcium transport twice as great in distal as in proximal small intestine. In the present study with brush border membrane vesicles from hamster, Vmax for saturable calcium transport was again twice as great in distal as in proximal small intestine. However, nonsaturable calcium transport rates relative to saturable rates were much greater with vesicles than in in vivo studies, and were greater in vesicles from distal than proximal small intestine. Since rates of saturable calcium uptake by brush border membrane vesicles parallel corresponding in vivo mediated transport rates, we conclude that the segmental rates of calcium transport in rat and hamster could be determined by brush border function.
Many questions remain unanswered
Authors: Michael Buckley
Journal: BMJ (2006)

create the risk that employers may shirk these important duties, leaving the task with GMC affiliates whose accounting lines are diffuse and unclear.The proposal meets neither the "better regulation" test of accountability, nor the requirement for transparency.We need to invest in and support the clinical governance role of health trusts.A regional profile for the GMC could add value here by encouraging dialogue and problem sharing within networks of medical directors and clinical governance leads.Under the new proposal, when an investigation by the Healthcare Commission or the ombudsman uncovers evidence that casts doubt on a doctor's fitness to practise, public interest demands that the matter be investigated.However, neither of these organisations has the facilities or capacity to investigate and prepare a case against a doctor.The doctor must therefore be investigated by the GMC before referral to an adjudication panel.Lively debate is ongoing over whether, once a doctor's case is before the GMC, the civil or the criminal standard of proof should be required.It seems unconscionable that a doctor be deprived of his or her right to practise and right to earn a living on the balance of probabilities.However, the regulators for teaching, social work, dentistry, and solicitors use the civil standard of proof.Legal commentators report that the civil standard is inherently a sliding scale, where the more serious the allegation, the more cogent the evidence required.We need to explore whether proportionalitythe concept of a sliding scale-can be reconciled with the need for consistency and fairness for all parties.
Abstract 5488: Granzyme B Contributes to Extracellular Matrix Degradation and Advanced Atherosclerotic Plaque Formation
Authors: Wendy A Boivin, Rani P Cruz, Hongyan Zhao, Pooja Rauniyar, David C Walker, Bruce M McManus, David J Granville
Journal: Circulation (2008)

Introduction: Granzyme B (GrB) is a cytotoxic serine protease that acts in chronic inflammation and disease through immune cell-mediated apoptosis and putatively through the degradation of extracel...
Choice of antidepressants: questionnaire survey of psychiatrists and general practitioners in two areas of Sweden
Authors: G. Isacsson, I. Redfors, D. Wasserman, U. Bergman
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b>: To identify factors that affect physicians9 choice of specific antidepressant drugs in order to evaluate the validity of epidemiological studies of the risks (particularly suicide) and benefits of different compounds. <b>Design</b>: Questionnaire survey of 264 psychiatrists and general practitioners in an urban area and a rural area of Sweden with validation of data by independent prescription surveys. <b>Setting</b>: Urban area of greater Stockholm and rural county of Jamtland, Sweden. Subjects—228 physicians (86%) who answered the questionnaire. <b>Main outcome measures</b>: The drugs used as first line drugs of choice, as drugs of choice in particularly severe depression, and as drugs of choice for disorders other than depression. <b>Results</b>: Amitriptyline was the most common first line drug of choice among both psychiatrists and general practitioners. The patterns of choice of antidepressants in the two areas accorded with prescribing patterns in two independent prescription surveys. Amitriptyline was chosen even more frequently for severe depression and depression with severe insomnia. Clomipramine was chosen comparatively more often for depression with severe anxiety. Low toxicity compounds (mainly lofepramine, mianserin, and moclobemide) were more often the drug of choice in depression associated with overt risk of suicide. Amitriptyline and clomipramine were used extensively for disorders other than depression (40% and 54% of prescriptions, compared with 13-19% for some other major antidepressants). <b>Conclusion</b>: Patient groups treated with different antidepressant compounds may not be comparable with respect to diagnoses and severity of disease. In particular, lofepramine, mianserin, and moclobemide, and possibly amitriptyline, seem to be chosen more often for patients prone to suicide.
A Specific Need for CRKL in p210BCR-ABL–Induced Transformation of Mouse Hematopoietic Progenitors
Authors: Ji-Heui Seo, Lisa J. Wood, Anupriya Agarwal, Thomas O'Hare, Collin R. Elsea, Ian J. Griswold, Michael W.N. Deininger, Akira Imamoto, Brian J. Druker
Journal: Cancer Research (2010)

CRKL (CRK-like) is an adapter protein predominantly phosphorylated in cells that express the tyrosine kinase p210(BCR-ABL), the fusion product of a (9;22) chromosomal translocation causative for chronic myeloid leukemia. It has been unclear, however, whether CRKL plays a functional role in p210(BCR-ABL) transformation. Here, we show that CRKL is required for p210(BCR-ABL) to support interleukin-3-independent growth of myeloid progenitor cells and long-term outgrowth of B-lymphoid cells from fetal liver-derived hematopoietic progenitor cells. Furthermore, a synthetic phosphotyrosyl peptide that binds to the CRKL SH2 domain with high affinity blocks association of endogenous CRKL with the p210(BCR-ABL) complex and reduces c-MYC levels in K562 human leukemic cells as well as in mouse hematopoietic cells transformed by p210(BCR-ABL) or the imatinib-resistant mutant T315I. These results indicate that the function of CRKL as an adapter protein is essential for p210(BCR-ABL)-induced transformation.
Sporting Activity and Hyperglycemia in Middle-Aged Men
Authors: Ivan J Perry, S Goya Wannamethee, Mark K Walker, A Gerald Shaper
Journal: Diabetes Care (1993)

OBJECTIVE To assess the relationship between self-reported frequency of participation in sporting activity and the prevalence of hyperglycemia (nonfasting glucose level &amp;gt; or = 7.8 mM) in middle-aged men. RESEARCH DESIGN AND METHODS We used a cross-sectional study of 7617 British middle-aged men, drawn from 24 general practices in England, Wales, and Scotland, who were participants in the British Regional Heart Study. The response rate was 78%. Patients with diabetes (physician-diagnosed) were excluded from our analysis. Frequency of participation in sporting activity was determined by the respondents and reported as none (61%), occasionally (12%), or frequently (27%). RESULTS The age-adjusted prevalence odds ratio for hyperglycemia was 0.86 (95% confidence interval, 0.6–1.2) in those reporting occasional, and 0.62 (95% confidence interval, 0.4–0.85) in those reporting frequent sporting activity, compared with those reporting none. This effect of frequent sporting activity on the prevalence of hyperglycemia was independent of body mass index, occupational status, smoking status, systolic blood pressure, use of antihypertensive therapy, and time of sampling. CONCLUSIONS Frequent sporting activity in middle-aged men is associated with a reduced prevalence of hyperglycemia and may reduce the risk of NIDDM.
Day-Case Anaesthesia and Sedation
Authors: D Rowbotham
Journal: BMJ (1994)

Ed J G Whitwam Blackwell Scientific, £49.50, p 424 ISBN 0-632-03704-0

Most hospitals have introduced day care services in the search for cost savings and reductions in waiting lists. Those that have merely decided to send for patients on the day of surgery and discharge them a few hours later are likely to find limited success, restless managers, and unhappy patients. Those that have appreciated that successful day care surgery and anaesthesia require major changes in organisation and patients' management are more likely to accept and enjoy the experience, as are …
Abstract 4931: Biomarker discovery in a large panel of cell lines shows different sample size requirement for prediction of response across a set of compounds
Authors: Michael Nebozhyn, Razvan Cristescu, Yaping Liu, Igor Feldman, Sergey Lezhnin, Theresa Zhang, Leigh Zawel, Stephen Fawell, Hongyue Dai, Jing Li, Andrey Loboda
Journal: Cancer Research (2012)

Abstract A panel of more than 600 cell lines from 17 tumor types has been profiled and sensitivity to a set of FDA approved compounds with different mechanisms of action has been tested. Comparison of gene expression profiles with overlapping set of publicly available profiles showed 100% accuracy of cell line identity prediction using nearest neighbor classifier. Similar analysis of CNV data had 80% accuracy due to relatively little CNV perturbation in some of the cell lines. Significant gene expression signatures have been detected for 80% of compounds. De-novo agnostic classification based on 50% train/test split and a linear classifier resulted in significant prediction on the test set for about 40% of the compounds, such as dasatinib, 5FU, paclitaxel, but failed to produce a significant prediction for others, such as doxorubicine, irinotecan, and vinblastine. For most of the compounds, the prediction of response is complex, with multiple distinct molecular features contributing to a classification algorithm. This inherent complexity requires integration of gene expression, CNV and mutation data as well as a large cell line sets for development of accurate classification algorithms. We defined functional CNV and SNV events using gene expression based modules as a functional readout. Predictive models that incorporate prior knowledge of mechanism of action of the compounds and rely on functional SNV and CNV events out perform completely agnostic methods of prediction. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4931. doi:1538-7445.AM2012-4931