tbuckley/cabot-search huggingface dataset:
New Drugs: Prescribing in old age
Authors: C. G Swift
Journal: BMJ (1988)

Secondly, expenditure on drugs for the elderly is proportionately greater. Figures from the Association of the British Pharmaceutical Industry for 1984 showed that of 315 million prescriptions, 77*6% were for people exempt from prescription charges, of whom about half were elderly. Thus 35-40% of drug expenditure is on the elderly (these figures relate to those of pensionable age), who constitute 15 16% of the total population. Thirdly, there is a disturbing apparent increase with age in susceptibility to adverse drug reactions. This has been more difficult to show historically but is an undoubted fact of life, particularly with certain drug groups such as several acting on the central nervous system, those with autonomie effects, and a variety of cardiovascular compounds. Information has been derived from anecdotal reports, expensive drug surveillance programmes in hospitals, detection systems for adverse drug reactions (such as the yellow card system of the Committee on Safety of Medicines), and reports on samples of selected patients, such as those being admitted to psychiatric units or departments of geriatric medicine. Underreporting and exploitation The extent to which age is perceived as conferring increased vulnerability may be positively weighted by the greater extent of prescribing but negatively weighted by a widespread failure to detect and diagnose iatrogenic disease in the elderly and by the underreporting of adverse reactions to regulatory bodies. Such underreporting is particularly likely where the adverse effect can be readily explained as an exaggeration of the drug's main action or one of its known side effects?that is, a type A or dose related effect. Many older people, particularly those who are disabled, tend to become reconciled to less than optimal health; hence neither they nor their carers complain readily, and the more subtle, if debilitat? ing, consequences of iatrogenic disorder are readily overlooked unless prescribers remain alert. The rapid growth in the numbers of new drugs means that special steps must be taken to protect the interests of this vulnerable and potentially exploitable section of the population, particularly as much pharmaceutical innovation is directly aimed at the relief of longstanding disorders prevalent within the age group rather than at radical short term cure. This paper will first, for completeness, outline the main areas of importance that have emerged from research into drugs in the elderly, though there are numerous recent reviews of the topic.17 Secondly, the possible implications for future prescribing, drug research, and drug development will be discussed.
Biocompatible photocrosslinked poly(ester anhydride) based on functionalized poly(ε-caprolactone) prepolymer shows surface erosion controlled drug release in vitro and in vivo
Authors: J. Mönkäre, R.A. Hakala, M.A. Vlasova, A. Huotari, M. Kilpeläinen, A. Kiviniemi, V. Meretoja, K.H. Herzig, H. Korhonen, J.V. Seppälä
Journal: Journal of Controlled Release (2010)
Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife.
Authors: M Van den Berg, L Birnbaum, A T Bosveld, B Brunström, P Cook, M Feeley, J P Giesy, A Hanberg, R Hasegawa, S W Kennedy, T Kubiak, J C Larsen, F X van Leeuwen, A K Liem, C Nolt, R E Peterson, L Poellinger, S Safe, D Schrenk, D Tillitt, M Tysklind, M Younes, F Waern, T Zacharewski
Journal: Environmental Health Perspectives (1998)

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in vivo evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties.
Thrombo-embolic complications of the cloth-covered Starr-Edwards prostheses No. 2300 aortic and No. 6300 mitral
Authors: J. Cleland, P. J. Molloy
Journal: Thorax (1973)

The thrombo-embolic complications of the cloth-covered Starr-Edwards prostheses No. 2300 aortic and No. 6300 mitral followed for an average of 14 months in 155 patients are reviewed. There was a high incidence of early fatal and disabling thrombo-embolus in patients having mitral valve replacement. Late emboli were more common after aortic valve replacement. Anticoagulant control was unsatisfactory and not without hazards.
Systematic Review: Enhancing the Use and Quality of Colorectal Cancer Screening
Authors: Debra J. Holden
Journal: Annals of Internal Medicine (2010)

Background: National guideline groups recommend screening and discussion of screening options for persons at average risk for colorectal cancer (CRC). However, emerging evidence suggests that CRC screening is simultaneously underused, overused, and misused and that adequate patient–provider discussions about screening are infrequent. Purpose: To summarize evidence on factors that influence CRC screening and strategies that increase the appropriate use and quality of CRC screening and CRC screening discussions. Data Sources: MEDLINE, the Cochrane Library, and the Cochrane Central Register of Controlled Trials were searched for English-language publications describing studies conducted in the United States from January 1998 through September 2009. Study Selection: Two reviewers independently selected studies that addressed the study questions and met eligibility criteria. Data Extraction: Information on study design, setting, intervention, outcomes, and quality were extracted by one reviewer and double-checked by another. Reviewers assigned a strength-of-evidence grade for intervention categories by using criteria plus a consensus process. Data Synthesis: Reviewers found evidence of simultaneous underuse, overuse, and misuse of CRC screening as well as inadequate clinical discussions about CRC screening. Several patient-level factors were independently associated with lower screening rates, including having low income or less education, being uninsured, being Hispanic or Asian, being less acculturated into the United States, or having limited access to care. Evidence that interventions that included patient reminders or one-on-one interactions (that is, between patients and nonphysician clinic staff), eliminated structural barriers (for example, simplifying access to fecal occult blood test cards), or made system-level changes (for example, using systematic screening as opposed to opportunistic screening) were effective in enhancing use of CRC screening was strong. Evidence on how best to enhance discussions about CRC screening options is limited. No studies focused on reducing overuse, and very few focused on misuse. Limitations: Reporting and publication bias may have affected our findings. The independent effect of individual elements of multicomponent interventions was often uncertain. Conclusion: Although CRC screening is underused overall, important problems of overuse and misuse also exist. System- and policy-level interventions that target vulnerable populations are needed to reduce underuse. Interventions aimed at reducing barriers by making the screening process easier are likely to be effective. Studies aimed at reducing overuse and misuse and at enhancing the quality and frequency of discussions about CRC screening options are needed. Primary Funding Source: Agency for Healthcare Research and Quality.
The Effect of Epidemic Measles on Immunization Rates
Authors: Karen P. Goldstein
Journal: JAMA (1996)

<h3>Objective.</h3> —To evaluate whether immunization against a vaccine-preventable disease is sought to avoid the naturally occurring disease itself, we hypothesized that the rate of "on-time" measles immunization would increase during an epidemic of that disease. If such an effect occurred, we wondered whether it would have an impact on on-time administration of other recommended immunizations. <h3>Design.</h3> —Retrospective evaluation of immunization rates of children at their second birthday with the use of computerized health records for children entering kindergarten in an 8-year interval spanning the onset of epidemic measles in Chicago, III, in 1989 and 1990. <h3>Setting.</h3> —Children entering Chicago public schools. <h3>Main Outcome Measures.</h3> —Rates of receipt of measles-containing vaccine (MCV), 1 to 4 doses of a diphtheria toxoid—tetanus toxoid—pertussis (DTP) or diphtheria toxoid—tetanus toxoid (DT) vaccine, 1 to 3 doses of oral or inactivated polio vaccine (OPV/IPV), and the full series of these vaccines (4:3:1) that are required to be "up-to-date" by the second birthday. <h3>Results.</h3> —The rate of on-time MCV receipt increased from 56% to 58% in the years prior to the epidemic to 70% during the epidemic (1989 and 1990). A similar increase did not occur for DTP/DT 4 or OPV/IPV 3. Moreover, among older children delayed in MCV receipt, evidence of catch-up immunization also occurred during the epidemic years; similar catch-up for delayed DTP/DT 4 or OPV/IPV 3 immunization did not occur. <h3>Conclusions.</h3> —Dramatic increases in on-time and catch-up MCV receipt occurred during the Chicago measles epidemic of 1989 and 1990. The lack of similar increases in DTP/DT 4 and OPV/IPV 3 suggests MCV receipt was not associated with receipt of other recommended immunizations during that time.
Treatment of Skin Carcinoma of the Face and Neck
Authors: Donald G. Lindsay
Journal: JAMA (1981)

<h3>To the Editor.—</h3> I would like to comment on the article by Chahin M. Chahbazian, MD, and G. Stephen Brown, MD (1980;244:1135). Radiation therapy of skin cancer is not "carefully chosen" nor "well planned" no matter how "meticulously administered," unless it is done with a consideration for the posttreatment result 20 to 25 years hence, the patient's complexion, the amount and type of subsequent sun exposure expected, and finally, the actual, not prejudicial, exposure of the patient to the possible surgical alternatives for his exact problem. In my opinion as a practicing dermatologist experienced in radiation therapy and as an instructor for several years in skin surgery at a large county hospital (Los Angeles County Hospital), radiation therapy of any kind has an extremely limited place in the treatment of skin carcinoma of the face and neck. Furthermore, it is virtually contraindicated for lesion in the inner canthus, the pinna
Treatment of irritable bowel syndrome
Authors: Michael J G Farthing
Journal: BMJ (2005)

Irritable bowel syndrome is characterised by diverse symptoms including abdominal pain, altered bowel function (increased bowel frequency, constipation), bloating, abdominal distension, the sensation of incomplete evacuation, and the increased passage of mucus. No unifying hypothesis explains all these symptoms, and no single agent will alleviate all components of the symptom complex. The currently favoured model to explain the symptoms includes central and end organ components. These may be combined into an integrated hypothesis that incorporates psychological factors (stress, distress, affective disorder) and dysfunction of the gut (disorders of motility, visceral hypersensitivity). Current standard drug treatment generally entails a symptom directed approach with drugs aimed at pain, constipation, and diarrhoea. Development of new drugs has focused mainly on agents that modify the effects of 5-hydroxytryptamine (5-HT) in the gut. Alternatives to this single receptor approach exist, although not all patients respond to educational and psychological interventions, and treatment with drugs will remain an option for non-responders.
Medical Education in Canada
Authors: Charles G. Roland
Journal: JAMA (1965)

Canada's problems in medical education result in part from the economic-geographic fact of Canada's small and dispersed population. Also pertinent is the influence of not one but several major schools of scientific thought: American, British, and French.  A group of distinguished Canadian educators, under the aegis of the Royal Commission on Health Services, prepared this report. The educators are all physicians; one is the dean of a faculty of medicine, three are former deans, and two, professors of medicine. The assessment was carried out between 1961 and 1964, and included visits to all Canadian medical faculties and new schools in other countries.  The authors analyze various facets of medical education: medical students, curriculum, medical schools, teaching hospitals, finance, training of teachers, postgraduate and continuing education, research, medical manpower, expansion of educational resources, and paramedical manpower. Medical-manpower problems receive particularly detailed scrutiny. After calculating the probable requirements for the next 30
NHS will pay for boy's proton beam therapy in Prague
Authors: C. Dyer
Journal: BMJ (2014)

Ashya King, the 5 year old boy whose parents fled abroad with him after a disagreement with doctors in Southampton over his treatment, is to have his proton beam therapy in Prague funded by England’s NHS.

Ashya’s parents, Brett and Naghmeh King, took him from Southampton General Hospital amid concerns about the side effects he might have after the standard radiotherapy that doctors said he needed after operating to remove a medulloblastoma.

The Kings left the hospital with Ashya without telling the doctors, as they were legally entitled to do in the absence of a court order. They were heading for Spain, with plans to sell the flat they owned near Malaga to …
Funding to improve health in poor countries needs to include local health systems
Authors: O. Mashta
Journal: BMJ (2009)

Benefits from unprecedented spending on public health in poor countries are being compromised by chronic underinvestment in health systems, according to a report led by the World Health Organization and published in the Lancet .

Although millions of people in recent years have benefited from the expansion of key global health initiatives, there is also evidence that such programmes can constrain the health systems of poor countries, says the Positive Synergies Health Policy report. And many opportunities to improve efficiency, equity, value for money, and outcomes in global public health are still being missed, it says.

Carissa Etienne, assistant director general …
Functional expression of Fas and Fas ligand on human gut lamina propria T lymphocytes. A potential role for the acidic sphingomyelinase pathway in normal immunoregulation.
Authors: R De Maria, M Boirivant, M G Cifone, P Roncaioli, M Hahne, J Tschopp, F Pallone, A Santoni, R Testi
Journal: Journal of Clinical Investigation (1996)

The expression and function of Fas (CD95/APO-1), a cell surface receptor directly responsible for triggering cell death by apoptosis, was investigated on human T lymphocytes resident within the intestinal lamina propria, a major site of antigen challenge and persistent lymphocyte activation. Three color immunofluorescence and FACS analysis indicated that virtually all freshly isolated human gut lamina propria T lymphocytes (T-LPL) express Fas, together with the marker of progress activation CD45R0. A discrete fraction of freshly isolated T-LPL also constitutively expressed Fas ligand (FasL), perhaps as a result of recent in vivo activation. Importantly, whereas Fas cross-linking did not result in apoptosis induction in peripheral blood T lymphocytes (T-PBL), Fas was found to be fully effective in generating the apoptotic signal in T-LPL. This was associated with the activation of an acidic sphingomyelinase and with ceramide generation, early events known to be involved in Fas-mediated apoptotic signaling. By contrast, acidic sphingomyelinase activation and ceramide production were not detectable in T-PBL after Fas cross-linking. However C2-ceramide, a cell permeant synthetic analog of ceramide, could efficiently induce apoptosis in T-LPL and T-PBL when added exogenously. These data indicate that T-LPL constitutively express both Fas and FasL and that Fas cross-linking generates signals resulting in sphingomyelin hydrolysis and apoptosis, outlining a potential mechanism involved in intestinal tolerance. Moreover, they provide the first evidence of a role for ceramide-mediated pathways in normal immunoregulation.
Circulatory Dynamics in Spontaneous and Nephrogenic Hypertensive Dogs during the Depressor Response to Acute Inflammation
Authors: J. STAMLER, A. P. FISHMAN, L. N. KATZ, S. RODBARD, A. Ellis, F. Williams
Journal: Circulation (1950)

Cardiac output and blood voluine are at control levels in unanesthetized hypertensive dogs during the depressor response to acute inflammation. Hence the fall in blood pressure is due to a decreased total peripheral resistance. The accompanying renal hyperemia indicates that decreased resistance in the renal vascular bed accounts for a significant portion of the fall in total peripheral resistance. Drug studies further suggest that acute inflammation operates to lower blood pressure in hypertensive dogs via mechanisms other than complete paralysis of autonomic vasomotor activity.
Patients With Malignancy Requiring Urgent Therapy
Authors: John K. Chan, Susan S. Lin, D. Scott McMeekin, Michael L. Berman
Journal: Journal of Clinical Oncology (2005)

6 to our knowledge to date, the present article is the first reported case of renal failure due to hypercalcemia in which biopsy has been performed.Hypercalcemia may induce renal failure, and physicians should be cognizant of this complication when elevated levels of serum PTHrP are detected in hypercalcemic patients with malignancy.
Withdrawal Depression in Obese Patients after Fenfluramine Treatment
Authors: J. M. Steel, M. Briggs
Journal: BMJ (1972)

Measurements of subjective feeling in 20 patients receiving fenfluramine alternating with placebo and in 19 patients receiving phentermine alternating with placebo indicated that depression of mood occurred four days after fenfluramine withdrawal but no such depression was seen with phentermine.
Development of the automated immunomonitoring system
Authors: Ryuji Osawa, Sachiko Yoshimura, Shoji Hisada, Koji Yoshida, Tsuyoshi Tojo, Hidenori Kuwata
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Cancer vaccine which induces cytotoxic T lymphocyte targeting tumor associated antigens is one of major stream in cancer immunotherapy. Many cancer immunotherapy programs are in the clinical development all over the world and also the identification of biomarker for
814-5 Perfusion and dilatation of old myocardial infarction improves after intracoronary autologous bone marrow stem cell transplantation
Authors: Athanassions Manginas, Dennis V Cokkinos, Evgenios Goussetis, Ioulia Peristeri, Maria Theodosaki, Stelios Graphakos, Evangelos Leontiadis, George Karatasakis, Maria Koutelou, Athanassios Theodorakos
Journal: Journal of the American College of Cardiology (2004)
III. CARDIOVASCULAR OBSERVATIONS
Authors: JAMES L. WHITNEY
Journal: JAMA (1918)

It has long been known that persons with defective hearts tolerate very badly such altitudes as those of Denver, Phoenix and Mexico City. Many instances have been quoted of serious and even fatal attacks of cardiac dilatation, pulmonary edema, etc., occurring within a few days after the arrival at these places. This popular view has, however, received up to the present very little confirmation from scientific work. Marked alterations in respiration have indeed been described; and the effects on the chemistry of the blood and tissues in reference to transport of oxygen have been studied in great detail. Beyond suggestions, however, that certain changes in blood flow might occur as the result of high altitudes, little evidence has been at hand that the effect on circulation is of great importance; especially there has been entire lack of proof of marked circulatory strain, or of the possibility of such disasters to
Genome-wide association study reveals class I MHC–restricted T cell–associated molecule gene (CRTAM) variants interact with vitamin D levels to affect asthma exacerbations
Authors: Rose Du, Augusto A. Litonjua, Kelan G. Tantisira, Jessica Lasky-Su, Shamil R. Sunyaev, Barbara J. Klanderman, Juan C. Celedón, Lydiana Avila, Manuel E. Soto-Quiros, Scott T. Weiss
Journal: Journal of Allergy and Clinical Immunology (2011)