tbuckley/cabot-search huggingface dataset:
279. A Novel Functionalized Polymeric Formulation for use in Delivering Therapeutic Genes for the Treatment of Solid Tumors
Authors: Jason Fewell, Majed Matar, Jennifer Rice, Gregory Slobodkin, Bruce Hovanes, Khursheed Anwer
Journal: Molecular Therapy (2005)

We have described the synthesis, physico-chemical properties and gene therapy application of a novel water soluble gene delivery system PEG-PEI-Chol (PPC). PPC is composed of a low molecular weight branched polyethyleneimine, cholesterol and polyethylene glycol and designed to promote DNA condensation into nanoparticles, enhance membrane uptake and improve biocompatibility and pharmacokinetics, respectively. The chemical composition and molar ratios between the individual components of the polymer were verified by NMR. Formulation of PPC with DNA produced particles of |[sim]|100nm mean diameter and zeta potential of |[sim]|20mV. In vitro optimization studies using a luciferase reporter gene were performed in order to evaluate the effects of varying amounts of PEG and increasing nitrogen to phosphorus ratio (N:P). Use of the PPC delivery system with a plasmid encoding for interleukin-12 (IL-12) for treatment of solid tumors was examined in mice. Significant inhibition in tumor growth rate and/or increased incidence of complete tumor rejection was seen in murine models of breast cancer and head and neck cancer following intratumoral injections. A combination therapy approach was evaluated where the IL-12/PPC treatment was combined with an investigative polymeric formulation of paclitaxel against 4T1 mammary tumors and it was shown that combined therapy led to a synergistic inhibition of tumor growth. This form of paclitaxel had little effect on SCCVII head and neck tumors however, cyclophosphamide strongly inhibited SCCVII tumor growth. Further, when IL-12/PPC intratumoral injections were combined with cyclophosphamide administration, there was a slight additional inhibition in tumor growth over the cyclophosphamide treatment alone and there was a significant increase in the rate of complete tumor rejection. Future studies will be aimed at optimizing dose and dosing regimens of combination therapies for the treatment of solid tumors.
Dysregulation of the C/EBPα Differentiation Pathway in Human Cancer
Authors: Steffen Koschmieder, Balazs Halmos, Elena Levantini, Daniel G. Tenen
Journal: Journal of Clinical Oncology (2008)

While much is known about aberrant pathways affecting cell growth and apoptosis, our understanding of another critical step of neoplastic transformation, differentiation arrest, remains poor. The differentiation-inducing transcription factor CCAAT enhancer binding protein alpha (C/EBPα) is required for proper control of adipogenesis, glucose metabolism, granulocytic differentiation, and lung development. Studies investigating the function of this protein in hematopoietic malignancies as well as in lung and skin cancer have revealed numerous ways how tumor cells abrogate C/EBPα function. Genetic and global expression analysis of acute myeloid leukemia (AML) cases identifies C/EBPα-deficient AML as a separate entity yielding novel classification schemes. In patients with a dysfunctional C/EBPα pathway, targeted therapies may overcome the block in differentiation, and in combination with conventional chemotherapy, may lead to complete eradication of the malignant clone. Overall, a better understanding of the mechanisms of how C/EBPα dysregulation participates in the neoplastic process has opened new gateways for differentiation biology research.
PATIENT INDUSTRY AND THE WORKERS' ATTITUDES TOWARDS THEIR JOBS
Authors: B. J. BOLIN, DOROTHY SCOTT
Journal: American Journal of Psychiatry (1958)

This survey of 148 (out of 623) patientindustry jobs and the patients' opinions about working leaves us with these impressions: 1. Work is one of the more favored activities among hospital patients; 2. Regular work raises the self-esteem of numerous patients; 3. A great many chronic patients retain the conviction that work is inherently worthwhile; 4. Work often relieves boredom or ameliorates distressing psychotic symptoms in these patients.
Focal Nodular Hyperplasia of the Liver Diagnosis by Dynamic and SPECT Scintigraphy
Authors: CHAN H. PARK, SUNG M. KIM, CHARLES INTENZO, JACK McEWAN, JAMES ZHANG
Journal: Clinical Nuclear Medicine (1993)

Focal nodular hyperplasia of the liver is a rare benign tumor usually found incidentally as an asymptomatic mass in young women. It is often confused with other lesions, particularly with hepatic cell adenoma. Differential diagnosis of these tumors is very important for their proper management. FNH is usually hypervascular and contains functioning Kupffer cells. The presence of Kupffer cells within the lesion can best be evaluated by SPECT and by comparing Tc-99m SC activity in the lesion to its activity in bone marrow. A young woman with right upper quadrant discomfort was evaluated by dynamic and SPECT using Tc-99m SC. Along with other imaging modalities such as ultrasonography, CT, and MRI, focal nodular hyperplasia was diagnosed noninvasively prior to surgery, which was necessary for her obstructive gastrointestinal symptoms.
P248 Legionella Pneumonia outbreak related to a display spa pool at a retail unit: Abstract P248 Table 1.
Authors: M Ahmed, V Laza-Stanca, N Mustfa
Journal: Thorax (2013)

<h3>Background</h3> Legionella pneumonia (LP) has been reported in a number of outbreaks in the UK. It has significant implications for public health as outbreaks require investigation to identify a responsible source. An outbreak of LP occurred in the Stoke-on-Trent area of North Staffordshire in July 2012. This is an analysis of the clinical cases reported and subsequent public health enquiry. <h3>Method</h3> Retrospective review of case records, pathology and radiology. Data was collated on clinical and biochemical features, microbiology and clinical outcome. Results of the public health enquiry were sourced from the local Health Protection Agency (HPA). <h3>Results</h3> 20 patients were confirmed to have LP. 13 male, 7 female. Mean age was 65 years. 50% were ex-smokers. 70% had at least two co-morbidities requiring treatment. 3 were immunosuppressed on longterm steroids. Only 1 patient reported foreign travel in the preceding month. Clinical, biochemical and radiological findings are shown in Table 1. Urinary legionella antigen was detected in all patients. Sputum PCR for legionella pneumophilia was positive in 8 cases and identified a single strain present in all samples (ST1268). Mean length of stay was 8.9 days. 6 patients (30%) required admission to intensive care for respiratory support; 2 were invasively ventilated. 18 patients were discharged home, 2 died. 65% had follow-up chest xrays showing improvement or resolution of consolidation. All cases were from the Stoke area. The HPA investigation detected the same legionella pneumophilia strain in a display spa pool at a retail unit, as found in the sputum. As no other tested sites were found to have this strain, it is very likely this was the origin of the local outbreak. All cases had visited the retail unit prior to their hospital admission. <h3>Conclusion</h3> LP remains a possible diagnosis in any case of community acquired pneumonia. This outbreak is a reminder that patients do not always present following the classic travel history. The diagnosis needs to be considered and vigilance in microbiological testing is necessary to identify potential cases.
GPs' time to be freed up under plans for increased choice
Authors: K. Burke
Journal: BMJ (2003)

Patients across England will be able to register with a GP near their work instead of home, pick up repeat prescriptions direct from their pharmacist, and attend nurse led clinics, under the government's flagship initiative to extend choice in the NHS.

Presenting a command paper before parliament on 9 December, the health secretary, John Reid, outlined the results of the national consultation on extending choice for patients.

Under a new general medical services contract, nurse led clinics and polyclinics (which offer a wide range of GP and specialist services) will be …
Studies of Bacterial Throat Flora during Chemoprophylaxis of Rheumatic Fever
Authors: Joseph M. Miller, Benedict F. Massell
Journal: New England Journal of Medicine (1956)

THE well established relation between acute rheumatic fever and antecedent infection due to Group A hemolytic streptococci has resulted in the widely accepted use of continuous daily chemoprophylaxis for the prevention of rheumatic fever in susceptible persons. The two agents that have demonstrated the most practical application for such prophylaxis are sulfadiazine and penicillin by mouth, and the use of these drugs has now undergone extensive clinical trial. Many workers have reported a low rate of occurrence of hemolytic streptococcal infections in children receiving chemoprophylaxis,1 2 3 4 5 6 7 8 9 10 11 12 but some questions persist regarding the potential dangers of such continuous prophylaxis.The possibility that . . .
Recollections and Reflections
Authors: David W. Sharp
Journal: JAMA (1988)

Photographs of Douglas Black belie the spare humor and charm of the man and of his writing. Even in wedding garb he looks morose. However, one snapshot here that did catch my eye was of young Douglas with his bicycle of the early 1920s. This two-wheeler is not obviously different from the steed that bore me in Cambridge (England) 40 years later. Why tinker with a basically sound design? That is Douglas Black's view of the provision of health care via a national health service and of the administration of medical research free from interference by a government department. Doctor, Professor, and now Sir, Douglas Black spent his working life in Manchester and London, and his thoughts on medicine and research, universities and government are shared in this, the second entry in the<i>British Medical Journal</i>'s Memoir Club. How health care should be provided and how medical research should
Memory CD4+ T cells: beyond “helper” functions
Authors: Kobporn Boonnak, Kanta Subbarao
Journal: Journal of Clinical Investigation (2012)

In influenza virus infection, antibodies, memory CD8+ T cells, and CD4+ T cells have all been shown to mediate immune protection, but how they operate and interact with one another to mediate efficient immune responses against virus infection is not well understood. In this issue of the JCI, McKinstry et al. have identified unique functions of memory CD4+ T cells beyond providing "help" for B cell and CD8+ T cell responses during influenza virus infection.
Comprehensive Textbook of Psychiatry, IV
Authors: Alan Stoudemire
Journal: JAMA (1986)

Study Guide and Self-examination Review for Modern Synopsis of Comprehensive Textbook of Psychiatry, IV,  by Harold I. Kaplan and Benjamin J. Sadock, ed 2; 551 pp, with illus, paper, $22.95, Baltimore, Williams & Wilkins, 1985.  Since the first edition of the Comprehensive Textbook of Psychiatry appeared in 1967, subsequent versions of the text have served to reflect the evolution of pyschiatry in further establishing its theoretical and scientific basis. The fourth edition in this series is generally consistent with this tradition, encapsulating the trends and significant advances that have occurred in the field as of mid-1983 to late 1983, when most of the chapters were written or revised. For example, the chapter on affective disorders has been expanded and reorganized and contains new sections on epidemiology, biochemistry, genetics, and pharmacotherapy, which provide comprehensive summaries of the wealth of recent psychiatric research in this area.  The chapters on child and adolescent
Those Deceptive Contraceptives
Authors: Edwin J. DeCosta
Journal: JAMA (1962)

DOCTOR, tell me about those new pills about which I hear so much. Is it true that I only have to take one daily for 20 days and I won't get pregnant? Is it true that they are harmless, and, if I wish, I can conceive later? Is it true that... ? Many questions could be asked and much of what the patient has heard is true, but there are aspects of oral contraception which have not been adequately discussed. It is not the purpose of this presentation to enter into the moral, sociological, philosophical, or religious pros and cons of contraception. Suffice to say that man has been interested in methods of birth control for a very long time; in fact, discussion and recommendations can be found in ancient Egyptian papyri. But it is only within the last few years that techniques have evolved which, because of their simplicity
DIVALENT CATION AND pH DEPENDENCE OF RAT INTRINSIC FACTOR ACTION IN EVERTED SACS AND MUCOSAL HOMOGENATES OF RAT SMALL INTESTINE*
Authors: Victor Herbert, William B. Castle
Journal: Journal of Clinical Investigation (1961)

In 1959 it was reported in these pages (1) that hog intrinsic factor concentrate enhanced the up- take of radioactive vitamin B12 (Co60-B12) by everted sacs of rat small intestine in the cold.This enhancement was significantly reduced in the absence of calcium and was reversible to a significant degree by disodium ethylenediamine tetraacetate dihydrate (EDTA) (1), suggesting that intrinsic factor action was calcium-dependent.Disodium EDTA reduced the enhancing effect on radio-Bl2 uptake of rat intrinsic factor in loops of small intestine in a living rat; calcium EDTA was without such inhibitory effect (2).Other workers, however, threw doubt on the calcium dependence of intrinsic factor action.They re- ported that gastrectomized rats fed radio-B12 bound to rat gastric juice plus large amounts of disodium EDTA (3, 4), and normal rats fed radio-B12 plus disodium or tetrasodium EDTA (5), had normal radio-B12 absorption.These findings, taken with the fact that the in vitro studies did not demonstrate total loss of the effect of intrinsic factor on depletion of calcium, left the concept of the calcium dependence of intrinsic fac- tor action in doubt.The present report presents the results of a study aimed at resolving this uncertainty, and also at strengthening the evidence (6, 7) for the pH dependence of intrinsic factor action. MATERIALS AND METHODSCo'-labeled vitamin B,2 and Co"1-labeled vitamin B,,.1The Co°-labeled vitamin B12 had a specific activity of ap- proximately 1 ,tc per /ug, and the Co"T-labeled vitamin B12
Energy expenditure and body composition in children with Crohn’s disease: effect of enteral nutrition and treatment with prednisolone
Authors: M Azcue, M Rashid, A Griffiths, P B Pencharz
Journal: Gut (1997)

Background —Malnutrition and growth retardation are common complications of Crohn’s disease in children. The contribution of resting energy expenditure (REE) to malnutrition is unclear. Aims —To characterise the REE and body composition in children with Crohn’s disease and compare them with normal controls and patients with anorexia nervosa; to compare the effects of prednisolone and enteral nutrition on energy expenditure and body composition. Subjects —Twenty four children with Crohn’s disease, 19 malnourished females with anorexia nervosa, and 22 healthy control subjects were studied. Methods —In children with Crohn’s disease measurements were done when the disease was acute and repeated at one and three months after treatment with either prednisolone or enteral nutrition. Resting energy expenditure was measured by indirect calorimetry and body composition by anthropometry, bioelectrical impedance analysis, total body potassium, H 2 18 O, and bromide space studies. Results —Body weight and ideal body weight were significantly lower in patients with Crohn’s disease than in healthy controls. Lean tissue was depleted and there was an increase in extracellular water. Per unit of lean body mass, there was no difference between REE in patients with Crohn’s disease and controls, whereas patients with anorexia nervosa had significantly reduced REE. With enteral nutrition all body compartments and REE increased significantly (p&lt;0.001). In a subgroup of age-matched men there was a significant increase in height after three months of enteral nutrition compared with prednisolone (p&lt;0.01). Those treated with steroids did not show a significant change in height but did show an increase in all body compartments. However, intracellular water as well as lean body mass accretion were significantly higher in the enteral nutrition group than in the prednisolone group. Conclusions —Despite being malnourished, children with Crohn’s disease fail to adapt their REE per unit of lean body mass. This might be a factor contributing to their malnutrition. Lean tissue accretion is higher in patients treated with enteral nutrition than in those treated with prednisolone.
Inhibition of JAK2 protects renal endothelial and epithelial cells from oxidative stress and cyclosporin A toxicity
Authors: Fernando Neria, Maria A. Castilla, Ruth Fernandez Sanchez, Francisco R. Gonzalez Pacheco, Juan J.P. Deudero, Olalla Calabia, Alberto Tejedor, Felix Manzarbeitia, Alberto Ortiz, Carlos Caramelo
Journal: Kidney International (2008)
Mortality is higher with drug eluting stents than with uncoated stents, studies find
Authors: Lisa Hitchen
Journal: BMJ (2006)

The safety of drug eluting stents has been called into question by two meta-analyses of their long term effects. The results of the studies were presented at the World Congress of Cardiology in Barcelona last week.

Both studies showed that the risk of death and of Q wave myocardial infarction, a clinical surrogate of stent thrombosis, was higher with drug eluting stents than with bare metal or uncoated stents.

The use by cardiologists of the first generation of drug eluting stents—the sirolimus (Cypher) and the paclitaxel (Taxus) stents—has risen rapidly since they were introduced. Currently around six million people worldwide have had a drug eluting stent fitted.

Their widespread uptake came after promising early data from a study published in the New England Journal of Medicine (2002;346:1773-80). This study showed that the rate of re-stenosis was zero at six months after implantation of drug eluting stents but 26% after implantation of bare metal stents. Other early studies indicated that stent thrombosis was not a problem with drug eluting stents.

However, four years later case reports of late stent thrombosis and delayed healing in patients fitted with …
Alpha-1 Antitrypsin Deficiency, Emphysema, and Cirrhosis in an Adult
Authors: KENNETH L. COHEN
Journal: Annals of Internal Medicine (1973)

The association between alpha-1 antitrypsin deficiency and cirrhosis has been described in children but not in adults. The liver from an adult with homozygous alpha-1 antitrypsin deficiency, emphysema, and cirrhosis was studied with fluorescent antibody specific for alpha-1 antitrypsin. The morphological findings from electron microscopy, fluorescent staining, and staining with periodic acid-Schiff reagent were similar to those found in the livers from children with alpha-1 antitrypsin deficiency and cirrhosis. The areas of greatest cellular damage contained the most alpha-1 antitrypsin. A deficiency of alpha-1 antitrypsin was associated with significant liver disease in this patient. More extensive evaluation of liver function and structure in adult patients deficient in alpha-1 antitrypsin is clearly indicated.
Gene Delivery: Nonendocytic Delivery of Lipoplex Nanoparticles into Living Cells Using Nanochannel Electroporation (Adv. Healthcare Mater. 5/2014)
Authors: Pouyan E. Boukany, Yun Wu, Xi Zhao, Kwang J. Kwak, Piotr J. Glazer, Kam Leong, L. James Lee
Journal: Advanced Healthcare Materials (2014)
Use of sorafenib in patients with hepatocellular carcinoma before liver transplantation: A cost-benefit analysis while awaiting data on sorafenib safety
Authors: Alessandro Vitale, Michael L. Volk, Davide Pastorelli, Sara Lonardi, Fabio Farinati, Patrizia Burra, Paolo Angeli, Umberto Cillo
Journal: Hepatology (2009)

The role of bridging therapies for patients with hepatocellular carcinoma (HCC) on the waiting list for liver transplantation (LT) remains controversial. There is strong evidence to support the effectiveness of sorafenib in extending the time to progression of HCC. Using a Markov model, we compared two strategies: one using sorafenib as neoadjuvant therapy before LT (Strategy A), and the other using no bridging therapy in the first 6 months (Strategy B). Reference case: T2 HCC patient with compensated cirrhosis. The benefit of sorafenib in delaying time to HCC progression was expressed as the hazard ratio (HR) and taken from recently published randomized trials. The endpoints considered were: survival benefit measured in quality-adjusted life days (QALDs), transplant probability, costs (C) in euro, willingness to pay (WTP), and net health benefit (NHB), where NHB = survival benefit - C/WTP. The calculated WTP of sorafenib in Italy was 346 euro per QALD. Probabilistic sensitivity analysis showed a median survival benefit of 94 QALDs (10% percentile = 38, 90% percentile = 210). In the base-case scenario (HR = 0.47, monthly dropout probability = 5%, median time to LT = 3 months), the gain in LT probability due to sorafenib was 5% and it increased proportionally with increasing median times to LT and decreasing HR. In the cost-benefit analysis, the incremental NHB of Strategy A versus Strategy B was 37 QALDs; it increased as sorafenib HR decreased and when median times to LT were shorter than 6 months, whereas for longer times it gradually dropped, particularly when Strategy B included effective locoregional treatments.Sorafenib neoadjuvant therapy is cost-effective by comparison with no therapy for T2-HCC patients waiting for LT, particularly for median times to LT under 6 months.
New research alliance for lung cancer is launched in London
Authors: J. Wise
Journal: BMJ (2013)

All patients in London with newly diagnosed lung cancer are to be offered genetic testing of their tumour and targeted treatments through a research programme that brings together leading research institutions and hospitals in the capital.

The London Lung Cancer Alliance, backed by England’s chief medical officer, Sally Davies, aims to transform the care of patients with lung cancer. Survival rates in the United Kingdom are worse than across much of Europe, with less …
Glycosuria of "Lag Storage" Type: an Explanation
Authors: R. D. Lawrence
Journal: BMJ (1936)

OSrickety deformities.He is mentally dull.During the years he has been in the sanatorium he has not changed much, but the disease is slowly progressing and the prognosis is unfavour- able; sputum 2 to 3 oz.daily.There is no family history of tuberculosis.For eight years he has drunk half a pint of raw milk daily.Cultures of tubercle bacilli were obtained from the sputum on three occasions, once in August and twice in November, 1934.The three strains were dysgonic (Class 2), and proved highly virulent for the rabbit.Each strain was injected intravenously into a rabbit, the doses ranging from 0.01 mg. to less than 0.001 mg. ; the rabbits died in 21, 34, and 61 days of typical severe general tuberculosis.