tbuckley/cabot-search huggingface dataset:
Resolving Ethical Dilemmas: A Guide for Clinicians
Authors: Bernard H. Adelson
Journal: JAMA (1995)

Dr Bernard Lo, the author of<i>Resolving Ethical Dilemmas: A Guide for Clinicians</i>, declares in his preface that "the goal of this book is to help clinicians resolve the mundane ethical issues in patient care as well as the dilemmas that keep them awake at night." I am persuaded that Dr Lo has achieved his goal and that, indeed, he delivers another important benefit: clinicians who sleep untroubled by concerns over ethical issues in their practice of medicine will, if they read and reflect upon this book, be sensitized to the fact that every aspect of clinical medicine confronts the health care worker with daily ethical issues. As professor of medicine and director of the Program in Medical Ethics at the University of California, San Francisco, School of Medicine, Dr Lo is eminently qualified to produce a guide for clinicians in the resolution of ethical dilemmas, and he has done
The Effectiveness of Rectal Administration of Insulin Suppository on Normal and Diabetic Subjects
Authors: Yoshimitsu Yamasaki, Motoaki Shichiri, Ryuzo Kawamori, Mikio Kikuchi, Toshihito Yagi, Sadao Arai, Ryohei Tohdo, Nobuyoshi Hakui, Nobuyoshi Oji, Hiroshi Abe
Journal: Diabetes Care (1981)

The effectiveness of insulin administration by rectal suppository was examined in normal and non-insulin-dependent nonobese diabetic subjects. A 100-U insulin suppository (mean 1.8 U/kg) given to the diabetic subjects caused four times as great a fall in plasma glucose compared with the normal subjects given the same dose (mean 1.6 U/kg). The insulin response after suppository administration demonstrated a significantly positive correlation (r = 0.83, P less than 0.01) with the plasma glucose level before administration. Diabetic subjects given a 100-U insulin suppository (mean 1.7 U/kg) 15 min after meals three times daily showed a significant (P less than 0.05) improvement in postprandial hyperglycemia accompanied by a restoration of the normal circadian profile of plasma IRI and a reduction of urinary glucose from 26 +/- 5.9 to 2.0 +/- 1.0 g/day. No untoward reactions were observed. These data strongly imply a unique characteristic of the insulin suppository in spite of low bioavailability.
Local councils call for more money for integrating care
Authors: M. Limb
Journal: BMJ (2014)

Local authorities have urged the UK government to inject extra funds into integration of health and social care, amid stark warnings that 2015-16 will be a crunch year for financial risks.

The Local Government Association has backed a proposal from the health think tank the King’s Fund for a new “transformation fund” to be created, as a senior NHS leader warned that NHS trusts’ finances could “go out of control” next year.

The association’s chairman, Merrick Cockell, said that about £2bn (€2.5bn; $3.3bn) was needed to ease short term disruption as new service models were created that would give people a “smooth care journey from diagnosis to treatment and beyond.” He also said the proposed Better Care Fund, comprising £3.8bn of council and NHS money pooled for closer working and reducing hospital admissions, which is due to come into effect next April, should be beefed up and made into a …
[525] EVALUATION OF EFFICIENCY OF SEQUENTIAL THERAPY WITH INTERFERON AND LAMIVUDINE FROM CHANGES OF HBV cccDNA IN LIVER IN HBeAg-POSITIVE CHRONIC HEPATITIS B PATIENTS
Authors: L.W. Zhuang, H.Y. Lu, C.W. Si, X.Y. Chen, Y. Chen, Z.H. Han, J.H. Xu, J. Li, Y.Y. Yu
Journal: Journal of Hepatology (2007)
Chakanambarth Mutteriyil Gopinath
Authors: Gopinath P
Journal: BMJ (2005)

Former general practitioner Harlow, Essex (b 1949; q Kasturba Medical College, south India, 1973; DOrth), died from a brain tumour on 6 November 2004.​2004.




Figure 1




Gopi worked as the district medical officer for Indian Southern Railways before coming to Britain in September 1979. After various training jobs he was a registrar in orthopaedics at Bedford Hospital for six years and completed an MSc in orthopaedics from the Royal National Orthopaedic Hospital, Stanmore. He then changed career to general practice, completing his training in St Neots. He became a principal in general practice in Harlow in 1997. He leaves a wife, Shashi, and two children.
400. Successful Production of Pseudotyped Mosaic rAAV Vectors Using a Modified Baculovirus Expression System
Authors: Erik Kohlbrenner, George Aslanidi, Kevin Nash, Stanislav Shklayev, Martha Campbell-Thompson, Barry J. Byrne, Richard O. Snyder, Nicholas Muzyczka, Kenneth H. Warrington, Sergei Zolotukhin
Journal: Molecular Therapy (2005)

Top of pageAbstract
Scalable production of rAAV vectors remains a major obstacle to the clinical application of this protypical gene therapy vector. A recently developed baculovirus-based production protocol (Urabe et al) found limited applications due to the system's design. Here we report a detailed analysis of the stability of the original baculovirus system components BacRep, BacVP, and transgene cassette-containing BacGFP. All of the baculovirus helpers analyzed were prone to passaging-dependent, loss-of-function deletions resulting in considerable decreases in rAAV titers. To alleviate the instability problem, we have modified the Rep-encoding component by splitting it into two separate vectors. Furthermore, we have examined the expression limits of the remaining components of this system in order to optimize its application to AAV vector production. In addition, to successfully employ this system to pseudotyped AAV vectors, we have introduced a novel modular approach of parvoviral phospholipase A2 (PLA2) domain swapping that allows for baculovirus production of infectious AAV8 based vectors. The novel chimeric rAAV2/8 vector, produced in Sf9 cells, incorporated AAV2 PLA2 into AAV8 capsid structure and was characterized by robust transduction in vivo. Finally, using the novel riboswitch-controlled gene expression system, we have constructed a universal Bac helper vector for producing infectious mosaic rAAV vector of any given serotype, as demonstrated for rAAV5 and rAAV8. The re-designed baculovirus system improves our capacity for rAAV production by making this AAV platform more applicable to other existing serotypes.
A Protective Gene for Graft-versus-Host Disease
Authors: Kenneth R. Cooke, James L.M. Ferrara
Journal: New England Journal of Medicine (2003)

Hematopoietic stem-cell transplantation is an effective but toxic therapy for a number of life-threatening diseases, especially hematologic cancers. The principal complication of allogeneic stem-cell transplantation (the transplantation of grafts from genetically different donors) is graft-versus-host disease (GVHD), which can occur despite aggressive immunosuppressive prophylaxis and even when the donor is a “perfectly” matched (HLA-identical) sibling. The complex pathophysiology of GVHD fundamentally depends on interactions between antigen-presenting cells of the recipient and mature T cells of the donor (see Figure). A substantial body of research in animal models has uncovered the contribution of cytokines to the inflammation and tissue damage that . . .
Transcriptomic Profiles and Circulating Tumor Cell Detection in Primary Breast Cancer.
Authors: F. Bidard, F. Reyal, F. Valet, C. Mathiot, E. Brain, F. André, M. Espié, R. Salmon, P. De Cremoux, F. Spyratos, M. Marty, J. Pierga
Journal: Cancer Research (2009)

Abstract Background: We have previously demonstrated that circulating tumor cells (CTC) detection by the CellSearch system is strongly associated with metastatic outcome in non-metastatic breast cancer (BC) treated by neoadjuvant chemotherapy (NACT) [Pierga, Clin Cancer Res 2008]. Transcriptomic analysis of primary tumors may uncover molecular phenotypes associated with CTC detection.Methods: Both CTC detection in blood at diagnosis and transcriptomic analysis of the primary tumor have been performed prospectively in 58 non-metastatic BC patients (pts) treated by NACT in a phase II trial (REMAGUS02). We searched for an association between CTC detection and (i) intrinsic molecular subtypes, (ii) stemness signature, (iii) other published signatures, and (iv) expression of molecular markers involved in CTC detection. CTC-associated genes were also studied (v).Results: (i) CTC detection was not statistically associated with an intrinsic molecular subtype: 29% in basal-like (n=5/17pts), 33% in HER2+ (3/9pts), 13% in luminal A (2/13pts), 20% in luminal B (2/10pts) and 29% in normal-like (2/7pts) BC. (ii) No association was found between CTC detection and the stemness signature. (iv) CTC detection was also not related to the “stemness profile”; it was independent of EpCAM, CK8 and CK18 transcriptomic expression. Other results (iii, v) will be disclosed at the meeting.Conclusion: Our study is the first to compare tumor gene expression profiles and blood dissemination of cancer cells in early BC pts. In these pts, CTC detection by the CellSearch system does not depend on intrinsic molecular subtypes, contrary to a published report based on in vitro-grown cells lines [Sieuwerts, J Natl Cancer Inst 2009]. Being independent from molecular prognostic factors, CTC detection is likely to play a critical role in early BC management.Supported by PHRC AOM/2OO2/02117, Pfizer inc., Roche, sanofi-aventis.ISRCTN10059974 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3005.
SALE OF PHYSICIANS' SAMPLES
Authors: Walter C. Allen
Journal: JAMA (1933)

<h3>To the Editor:</h3> —May I call your attention to a possible new "racket"; certainly it was brand new for me: A man came into my office, very well dressed, and wanted to buy any "physicians' samples" I had on hand. I told him I had none on hand. He then wanted to know if he might call at some future time for any samples I might have. I didn't invite him to do so, but I did inquire as to what possible use he might have for them, and he said that there was a sale for them. Pharmaceutic manufacturers would hardly care to have the samples which they have left in the hands of physicians disposed of in this way. There must be some angle to all this which is not apparent on the surface. If this is a practice carried out on a wide scale in numerous cities,
Carbonic Anhydrase IX Promotes Tumor Growth and Necrosis<i>In Vivo</i>and Inhibition Enhances Anti-VEGF Therapy
Authors: Alan McIntyre, Shalini Patiar, Simon Wigfield, Ji-liang Li, Ioanna Ledaki, Helen Turley, Russell Leek, Cameron Snell, Kevin Gatter, William S. Sly, Richard D. Vaughan-Jones, Pawel Swietach, Adrian L. Harris
Journal: Clinical Cancer Research (2012)

Bevacizumab, an anti-VEGFA antibody, inhibits the developing vasculature of tumors, but resistance is common. Antiangiogenic therapy induces hypoxia and we observed increased expression of hypoxia-regulated genes, including carbonic anhydrase IX (CAIX), in response to bevacizumab treatment in xenografts. CAIX expression correlates with poor prognosis in most tumor types and with worse outcome in bevacizumab-treated patients with metastatic colorectal cancer, malignant astrocytoma, and recurrent malignant glioma.We knocked down CAIX expression by short hairpin RNA in a colon cancer (HT29) and a glioblastoma (U87) cell line which have high hypoxic induction of CAIX and overexpressed CAIX in HCT116 cells which has low CAIX. We investigated the effect on growth rate in three-dimensional (3D) culture and in vivo, and examined the effect of CAIX knockdown in combination with bevacizumab.CAIX expression was associated with increased growth rate in spheroids and in vivo. Surprisingly, CAIX expression was associated with increased necrosis and apoptosis in vivo and in vitro. We found that acidity inhibits CAIX activity over the pH range found in tumors (pK = 6.84), and this may be the mechanism whereby excess acid self-limits the build-up of extracellular acid. Expression of another hypoxia inducible CA isoform, CAXII, was upregulated in 3D but not two-dimensional culture in response to CAIX knockdown. CAIX knockdown enhanced the effect of bevacizumab treatment, reducing tumor growth rate in vivo.This work provides evidence that inhibition of the hypoxic adaptation to antiangiogenic therapy enhances bevacizumab treatment and highlights the value of developing small molecules or antibodies which inhibit CAIX for combination therapy.
Left Pulmonary Artery from Ascending Aorta in Tetralogy of Fallot
Authors: JACOB R. MORGAN
Journal: Circulation (1972)

Reported is the first surgically corrected case of tetralogy of Fallot with anomalous origin of the left pulmonary artery from the ascending aorta. The diagnosis of origin of the left pulmonary artery from the aorta depends on an aortogram, but clinical hints are increased vascularity in the left lung compared with the right lung and a continuous murmur. In tetralogy of Fallot, when there is late filling of the left pulmonary artery after a right ventricular cineangiogram, anomalous origin of the left pulmonary artery should be suspected and confirmed by an aortogram. Differentiation from complete absence of the left pulmonary artery, which is also often associated with tetralogy of Fallot, is possible by chest roentgenogram.
Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter trial
Authors: Dieter Hoelzer, Jan Walewski, Hartmut Döhner, Andreas Viardot, Wolfgang Hiddemann, Karsten Spiekermann, Hubert Serve, Ulrich Dührsen, Andreas Hüttmann, Eckhard Thiel, Jolanta Dengler, Michael Kneba, Markus Schaich, Ingo G. H. Schmidt-Wolf, Joachim Beck, Bernd Hertenstein, Albrecht Reichle, Katarzyna Domanska-Czyz, Rainer Fietkau, Heinz-August Horst, Harald Rieder, Stefan Schwartz, Thomas Burmeister, Nicola Gökbuget
Journal: Blood (2014)
Perioperative acute kidney injury: risk factors, recognition, management, and outcomes
Authors: E. Borthwick, A. Ferguson
Journal: BMJ (2010)

#### Summary points

Perioperative acute kidney injury (AKI) is common but poorly recognised and managed

Perioperative AKI increases surgical mortality and morbidity and increases cost

An apparently successful surgical outcome may not mean a successful renal outcome

Careful and thoughtful preoperative assessment, including identifying patients with existing chronic kidney disease and stopping and avoiding nephrotoxic drugs, will reduce the incidence of perioperative AKI.

Management of AKI centres on optimising fluid status and blood pressure, treating sepsis, and removing nephrotoxic agents where possible

Patients with AKI are often complex to treat, and senior help should be sought at an early stage

Acute kidney injury (AKI), formerly known as “acute renal failure,” is associated with increased morbidity, mortality, duration of hospital stay, and healthcare cost.w1 Despite this, published data on perioperative acute kidney injury, occurring between the time of admission for surgery and the time of discharge, are scarce outside the cardiovascular surgery setting. Regardless of the clinical setting, the diagnosis of AKI is often delayed, and treatment is suboptimal in a large proportion of cases.1 To improve diagnosis and treatment, clinicians need to understand the risks and triggers for perioperative AKI, the association of even small transient rises in creatinine concentration with risk of death,2 and what actions they need to take promptly on diagnosis. The term acute kidney injury reflects the importance of thinking of the condition as a spectrum or continuum of disease that may be recognised at an early stage, rather than as an “all or nothing” phenomenon as implied by the term acute renal failure. Recognising earlier stages of renal impairment allows for early appropriate action that may interrupt a process of functional decline. 

In this article we recommend the introduction of systems to ensure that changes in creatinine concentration from baseline are urgently highlighted to the …
Impact of Free Vaccine and Insurance Status on Physician Referral of Children to Public Vaccine Clinics
Authors: Richard Kent Zimmerman
Journal: JAMA (1997)

Concerns about financial barriers to vaccination led to the development of the Vaccines for Children (VFC) program, which provides free vaccines to states for children who are uninsured, Medicaid eligible, or Native American or Native Alaskan.To understand the effect of economic factors on physician likelihood of referring children to public vaccine clinics for immunizations and to evaluate the VFC program.A standardized survey was conducted in 1995 by trained personnel using computer-assisted telephone interviewing.A stratified random sample of family physicians, pediatricians, and general practitioners younger than 65 years who were in office-based practices across the United States.Likelihood of referral of a child to a health department for vaccination by child's insurance status and by the physician's receipt of free vaccines.Of the 1769 physicians with whom an interviewer spoke, 1236 participated. Most respondents (66%) were likely to refer an uninsured child to the health department for vaccination, whereas only 8% were likely to refer a child who had insurance that covers vaccination. The majority (58%) of physicians reported differential referral based on insurance status. Among physicians who received free vaccine supplies from the VFC program or elsewhere, 44% were likely to refer an uninsured child whereas 90% of those not receiving free vaccine were likely to refer the same child (P<.001). In regression analysis, the receipt of free vaccine supplies accounted for 24% of the variance in the likelihood to refer an uninsured child for vaccination.Physicians receiving free vaccine supplies report being less likely to refer children to public clinics for vaccinations.
Enhancement of influenza virus infections by secalonic acid D.
Authors: D S Fleischhacker, T G Akers, S P Katz, M S Palmgren
Journal: Environmental Health Perspectives (1986)

Secalonic acid D (SAD), a hepatotoxic, teratogenic, and slightly mutagenic metabolite of Penicillium oxalicum has been identified as a natural contaminant of grain dust. Secalonic acid D was administered intraperitoneally to male ICR mice that were exposed to influenza virus aerosols 5 days earlier. The mortality rate was significantly higher (p less than 0.001) in mice subjected to both influenza and SAD than those subjected to influenza alone. Virus titers in lung tissue samples at selected time intervals appeared similar for both influenza and influenza-SAD treated groups of mice for 9 days after exposure to the virus. After 9 days, influenza-SAD treated mice appeared to have higher virus titers. No difference in the pathological progression of pneumonia was discernible between these two groups of mice. The influenza-SAD group, in addition to pneumonia, exhibited severe hepatic necrosis characteristic of SAD administration. Mice infected with influenza virus followed by administration of SAD responded with significantly lower (p less than 0.05) antibody titers to influenza virus than mice exposed to influenza virus alone.
Consequences of the 1989 New York State Triplicate Benzodiazepine Prescription Regulations
Authors: Michael Weintraub
Journal: JAMA (1991)

Comparison of psychoactive medication prescribing and Medicaid expenditures before (1987 through 1988) and after (1989 through 1990) institution of the New York State triplicate benzodiazepine regulations.The National Prescription Audit (IMS America, Plymouth Meeting, Pa), New York State Medicaid, and Blue Cross/Blue Shield fo the Rochester (NY) Area.From 1988 to 1989, New York State benzodiazepine prescribing decreased by 44%, 60%, and 30% as assessed by IMS America, Medicaid, and Blue Cross/Blue Shield, respectively. Prescribing of the following alternative sedative-hypnotics increased in New York State compared with decreases nationally (IMS America data): meprobamate, +125% vs -9%; methyprylon, +84% vs -15%; ethchlorvynol, +29% vs -18%; butabarbital, +31% vs -15%; hydroxyzine, +15% vs -1.1%; and chloralhydrate, +136% vs -0.4%. Increased prescribing of alternatives was also seen in the Medicaid and Blue Cross/Blue Shield data. Medicaid benzodiazepine expenditures decreased 52% from 1988 to 1989 ($21.7 million to $10.4 million). Alternative sedative expenditures increased 115% ($3.9 million to $8.4 million). Total Medicaid psychoactive medication expenditures remained nearly constant ($46.7 million to $45.6 million).Although the triplicate regulations have decreased benzodiazepine prescribing, an undesirable increase has occurred in the prescribing of less acceptable medications. The wider public health, patient care, and financial implications of triplicate benzodiazepine regulations are of concern and require further study before other jurisdictions undertake similar programs.
Psychosocial Interaction from the Patients Point of View – Patient Satisfaction by CPQ-BC (Cologne Patient Questionnaire – Breast Cancer) in 51 German Breast Centers.
Authors: R. Wuerstlein, P. Steffen, C. Kowalski, M. Alich, M. Warm, H. Pfaff, N. Harbeck
Journal: Cancer Research (2009)

Abstract Background: The implementation of breast centers aims at improving the quality of care for breast cancer patients. Hereby the quality of psychosocial interaction from doctors and nursing staff is an essential aspect for patient satisfaction. This presentation based on empirical data shows the quality of psychosocial interaction from the point of view of patients in 51 german breast centers and if it has changed in annual comparison. Moreover, it analyses how the individual breast centers differ from each other and gives benchmarking data as well as data concerning the increasing significance attributed by patients to the assessment of quality of care and patient satisfaction.Material and Methods: Basis for the data is a retrospective survey of 10837 newly diagnosed breast cancer patients after primary surgery between 2006 and 2008 in 51 breast centers in Germany. After being inpatients, they were sent the specially developed Cologne Patient Questionnaire for Breast Cancer (CPQ-BC) which comprises key data to relevant aspects of psychosocial interaction such as support from physicians or nursing staff, doctor facilitation scale, patient information scale, patient participation in decision making, empathic provision of information, provision of information by physicians (basic and additional information), physical functioning, psychological well-being and tendency to excuse.Results: 88% of the contacted patients returned a completed questionnaire. The results of the descriptive analyses show that the quality of psychosocial interaction in the breast centers was overall evaluated very positively and that it is relatively stable in three years time. However, there are clear differences between the individual centers.Discussion: We noted that the quality of psychosocial interaction in the german breast centers already has a high standard from the patients point of view. This standard needs to be maintained and developed further. Moreover, the declared aim should be to dismantle the existing differences in quality between the centers. A specific evaluation of various structure and process features can give information on the reasons for these differences. Benchmarking data and specially developed benchmarking workshops help breast centers and their teams to improve quality of care and provide a good psychosocially supportive provider-patient interaction. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1071.
Continual Exposure to Cigarette Smoke Extracts Induces Tumor-Like Transformation of Human Nontumor Bronchial Epithelial Cells in a Microfluidic Chip
Authors: Encheng Li, Zhiyun Xu, Fen Liu, Huiling Wang, Jiabin Wen, Shujuan Shao, Lichuan Zhang, Lei Wang, Chong Liu, Jianxin Lu, Wenxin Wang, Zhancheng Gao, Qi Wang
Journal: Journal of Thoracic Oncology (2014)