tbuckley/cabot-search huggingface dataset:
"Orphan Drugs" for the Third World
Authors: HAROLD J. SIMON
Journal: Annals of Internal Medicine (1981)

Editorials1 August 1981"Orphan Drugs" for the Third WorldHAROLD J. SIMON, M.D., PH. D.HAROLD J. SIMON, M.D., PH. D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-95-2-231 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn their policy discussion paper in this issue, "Orphan Drugs: Creating a Policy," Asbury and Stolley (1) direct attention to a study of drugs of limited commercial interest recently completed by an interagency task force under the aegis of the Department of Health and Human Services (formerly Health, Education, and Welfare) and to a published summary of the task force's conclusions and recommendations (2). Although the report focuses on problems with the most obvious category of "orphan drugs," drugs for rare diseases, it also briefly mentions "drugs for use in diseases endemic to the third world countries (nonpaying customers with...References1. ASBURYSTOLLEY CP. Orphan drugs: creating a policy. Ann Intern Med. 1981;95:221-4. LinkGoogle Scholar2. FINKEL M. Drugs of limited commercial value. N Engl J Med. 1980;302:643-4. CrossrefMedlineGoogle Scholar3. . Pharmaceuticals for Developing Countries. Washington, D.C.: National Academy Press; 1979. Google Scholar4. . Pharmaceutical Innovations and the Needs of Developing Countries. Washington, D.C.: National Academy of Sciences; 1979. (National Academy of Sciences Policy Paper). Google Scholar5. SIMON H. Pharmaceuticals for developing countries. . In: NATIONAL RESEARCH COUNCIL. Current Issues and Studies. Washington, D.C.: National Research Council; 1979. Google Scholar6. MANSOUR T. Chemotherapy of parasitic worms: new biochemical strategies. Science. 1979;205:462-9. CrossrefMedlineGoogle Scholar7. COHEN S. Comparative biochemistry and drug design for infectious disease. Science. 1979;205:964-71. CrossrefMedlineGoogle Scholar8. MCDERMOTT W. Pharmaceuticals: their role in developing societies. Science. 1980;207:240-5. CrossrefGoogle Scholar9. SIMON H. Pharmaceuticals for developing countries: an interface of science, technology, and public policy. Pharos. 1981;44(2):9-15. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: School of Medicine University of California at San Diego La Jolla, California PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDoes orphan drug legislation really answer the needs of patients?Orphan drugs: legal aspects, current situation 1 August 1981Volume 95, Issue 2Page: 231-232KeywordsDrug policyDrugs Issue Published: 1 August 1981 PDF downloadLoading ...
Comparison of Indices of Vitamin A Status in Children With Chronic Liver Disease *
Authors: Andrew P. Feranchak, Jane Gralla, Robert King, Rebecca O. Ramirez, Mary Corkill, Michael R. Narkewicz, Ronald J. Sokol
Journal: Hepatology (2005)

Abstract Malabsorption of fat-soluble vitamins is a major complication of chronic cholestatic liver disease. The most accurate way to assess vitamin A status in children who have cholestasis is unknown. The goal of this study was to assess the accuracy of noninvasive tests to detect vitamin A deficiency. Children with chronic cholestatic liver disease (n = 23) and noncholestatic liver disease (n = 10) were studied. Ten cholestatic patients were identified as vitamin A–deficient based on the relative dose response (RDR). Compared with the RDR, the sensitivity and specificity to detect vitamin A deficiency for each test was, respectively: serum retinol, 90% and 78%; retinol-binding protein (RBP), 40% and 91%; retinol/RBP molar ratio, 60% and 74%; conjunctival impression cytology, 44% and 48%; slit-lamp examination, 20% and 66%; tear film break-up time, 40% and 69%; and Schirmer's test, 20% and 78%. We developed a modified oral RDR via oral coadministration of d-alpha tocopheryl polyethylene glycol-1000 succinate and retinyl palmitate. This test had a sensitivity of 80% and a specificity of 100% to detect vitamin A deficiency. In conclusion , vitamin A deficiency is relatively common in children who have chronic cholestatic liver disease. Our data suggest that serum retinol level as an initial screen followed by confirmation with a modified oral RDR test is the most effective means of identifying vitamin A deficiency in these subjects. (Hepatology 2005;42:782–792.)
Metabolic Effects of Oestrogen Treatment in Patients with Carcinoma of Prostate: A Comparison of Stilboestrol and Conjugated Equine Oestrogens
Authors: M. Shahmanesh, C. H. Bolton, R. C. L. Feneley, M. Hartog
Journal: BMJ (1973)

Serum cholesterol and triglyceride levels were estimated and oral glucose tolerance tests performed on 16 patients with carcinoma of the prostate before treatment and while receiving stilboestrol in doses of 1 mg, 7·5 mg, and 15 mg daily and conjugated equine oestrogens (Premarin) 15 mg daily. Serum triglyceride levels were greater than 170 mg/100 ml in nearly all the patients while receiving Premarin or stilboestrol 7·5 mg and 15 mg daily. In six out of 10 patients who were given stilboestrol 1 mg daily the serum triglycerides remained within the normal range. No significant effects on serum cholesterol levels or glucose tolerance tests were observed with the various oestrogen regimens. The results support previous suggestions that a daily dose of 1 mg of stilboestrol should be regularly used in the treatment of carcinoma of the prostate.
EPILEPSY ASSOCIATED WITH HYPERINSULINISM
Authors: Marvin Sandorf
Journal: JAMA (1933)

To the Editor:  —InThe Journal, February 4, page 321, is an article entitled Epilepsy and Narcolepsy Associated with Hyperinsulinism, by Dr. Searle Harris of Birmingham, Ala. These cases are interesting. Since 1924, when Dr. Harris reported the first case of hyperinsulinism associated with epilepsy, many more cases have been reported inThe Journal. Since 1929 I have been studying such cases and have made the following observations: 1. These patients, regardless of the type of epilepsy, show a low blood sugar; especially is this true prior to the epileptic seizure. These blood sugars range from 35 to 65 mg. per hundred cubic centimeters of blood. 2. Low blood sugars mean an anoxemia, alkalosis and edema of the brain, which increases the possibility of convulsions. 3. High blood sugars mean acidosis and dehydration, which decrease the possibility of convulsions. 4. In trying to increase the blood sugar of epileptic patients,
Alternative task construals, computational escape hatches, and dual-system theories of reasoning
Authors: Linden J. Ball, Jeremy D. Quayle
Journal: Behavioral and Brain Sciences (2000)

Stanovich &amp; West's dual-system represents a major development in an understanding of reasoning and rationality. Their notion of System 1 functioning as a computational escape hatch during the processing of complex tasks may deserve a more central role in explanations of reasoning performance. We describe examples of apparent escape-hatch processing from the reasoning and judgement literature.
Adverse reactions to intravenous thiopentone.
Authors: H J Lewi, T V Taylor
Journal: BMJ (1977)

continuing and expanding research on the treatment of this condition, which is at present responsible for considerable personal distress and social disruption.In view of the large numbers of women between the menarche and the menopause who suffer from PMS any significant reduction in its overall incidence will be welcome and we hope that family doctors will be encouraged to treat PMS by these new approaches.Further help and support from specialised clinics in teaching hospitals and other centres will be required for some time yet, but we hope soon to publish further observations on the clinical presenta- tion of PMS which will minimise this need.
935-36 Mechanism of Benefit of Stenting in Failed PTCA. Final Results from the Trial of Angioplasty and Stents In Canada (TASC II)
Authors: Simon G. Ray, Ian M. Penn, Donald R. Ricci, Jacques Barth, G.B. John Mancini, Christopher E. Buller, Blair O’Neill, Christopher Foster, David Almond, Charles Lazzam, Louis Roy, Gerald Barbeau
Journal: Journal of the American College of Cardiology (1995)
Prescribing information for patients.
Authors: J Williams
Journal: BMJ (1978)

Blood pressure was measured in a birth cohort of 5362 subjects at the age of 36. The prevalence of hypertension in men (blood pressure greater than 140/90 mm Hg) was almost twice that in women, although women received treatment more often. Deaths of fathers of subjects from hypertensive and ischaemic heart disease were associated with significantly higher mean systolic and diastolic pressures in both sexes. Cigarette smoking was not strongly associated with blood pressure in men and not associated at all in women. Of the social factors, low social class of family of origin was associated with high blood pressure in both sexes; but the strongest association was with current body mass, and birth weight also contributed. Differences in blood pressures between the sexes may have been related to protective biological factors, such as endogenous sex hormones, in women and also to differences in types of employment, smoking habits, and body mass. Differences in blood pressures related to the social class of family of origin may reflect long term influences of class differences on diet, exercise, and educational achievement. The importance of measuring secular trends in obesity and blood pressures is emphasised.
Andrew Henderson Torrance
Authors: Keith Torrance
Journal: BMJ (2004)

Former general practitioner Hugglescote, Leicestershire (b 1918; q St John's College, Oxford, 1943; FRCGP), d 10 March 2004.​2004.




Figure 1




Andrew's first job after graduating was at Leicester Royal Infirmary. In 1946 he and his young bride, Dr Lorna Lawrence Duncan, bought a two handed practice at Hugglescote, Leicestershire, just a couple of miles from where he was born. He expanded the practice, finally retiring in 1988. Andrew was president of Leicestershire Medical Society in 1987 and secretary of West Leicestershire Medical Society. Predeceased by his wife, he leaves three children and eight grandchildren.
Computer Procedure as Aid in Diagnosis
Authors: R. J. Nertney
Journal: JAMA (1963)

<h3>To the Editor:—</h3> The article titled "Conditional Probability Program for Diagnosis of Thyroid Function" by Overall and Williams (<i>JAMA</i><b>183</b>:5 [Feb 2] 1963) was timely and well written. I believe, however, it should be indicated that, in clinical application, such procedures may function as useful "aids" to the practicing physician in focusing his attention on the more probable diagnoses. The emphasis on the word "aid" is necessary for two reasons. First, the practicing physician has a natural and proper reluctance to accept any system in which his diagnostic acumen is apparently replaced by a computer. This misapprehension can delay acceptance of these methods in proper context. The second aspect is a serious functional one which I have encountered in application of a somewhat similar method to the control of industrial work groups. The problem in this case is the result of a phenomenon which we call "depersonalization." That is
AFIP:Pathology Laboratory to the World
Authors: Beverly Merz
Journal: JAMA (1989)

THERE ARE 2700 BRAINS at the Armed Forces Institute of Pathology (AFIP). Seven hundred are engaged in running the institute; 2000 are sectioned and mounted. The 125 pathologists and their 575 staff associates at the Walter Reed-based facility are entrusted with the Yakovlev Collection, the world's largest collection of serially sectioned human brains. But that's only one facet of their job. They oversee 2 200 000 case reports that have accumulated since the institute was established; they account for 350 publications in the scientific literature annually; they handle 350 consultations each day; they spend 60 000 person-days a year training pathologists; and they administrate an annual budget of more than $35 million. If the Smithsonian Institution is the nation's attic, the AFIP may be considered its morgue. Its role as such dates to the inception of its antecedent, The Army Medical Museum, in 1862. That institution was born of a
C-Reactive Protein Accelerates the Progression of Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Antoni Paul, Kerry W.S. Ko, Lan Li, Vijay Yechoor, Mark A. McCrory, Alexander J. Szalai, Lawrence Chan
Journal: Circulation (2004)

Plasma C-reactive protein (CRP) concentration is a strong predictor of atherosclerosis. However, to date, there is no in vivo evidence that CRP is proatherogenic.We studied the effect of human CRP transgene (tg) expression, under basal and turpentine-stimulated conditions, on atherosclerosis in apolipoprotein (apo) E-/- mice. Aortic atherosclerotic lesions in 29-week-old male mice were 48% larger (P<0.02) in turpentine-treated mice and 34% larger (P<0.05) in untreated CRPtg+/0/apoE-/- mice. Turpentine treatment per se did not affect the extent of atherosclerosis in CRP transgenic or nontransgenic apoE-/- mice. Transgenic mice exhibited lower plasma complement C3 but increased deposition of CRP and C3 in the lesions, which suggests that CRP stimulated activation of complement within the lesion. There was more intense and widespread vascular cell adhesion molecule-1 and collagen staining in the lesions of CRPtg+/0/apoE-/- mice than in CRPtg0/0/apoE-/- littermates. Lesions of CRPtg+/0/apoE-/- mice contained increased angiotensin type 1 receptor (AT1-R) transcripts and displayed increased AT1-R immunostaining compared with those of CRPtg0/0/apoE-/- mice. There was no difference in blood pressure in the 2 types of mice, which indicates that the proatherogenic effect of CRP-associated AT1-R overexpression is local and not mediated by its hypertensive properties.Human CRP transgene expression causes accelerated aortic atherosclerosis in apoE-/- mice. CRP was detected in the lesion, which was associated with increased C3 deposition and increased AT1-R, vascular cell adhesion molecule-1, and collagen expression. These data document a proatherogenic role for CRP in vivo.
Computer support for recording and interpreting family histories of breast and ovarian cancer in primary care (RAGs): qualitative evaluation with simulated patients
Authors: J. Emery, R. Walton, A. Coulson, D. Glasspool, S. Ziebland, J. Fox
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives:</b> To explore general practitioners9 attitudes towards and use of a computer program for assessing genetic risk of cancer in primary care. <b>Design:</b> Qualitative analysis of semistructured interviews and video recordings of simulated consultations. <b>Participants:</b> Purposive sample of 15 general practitioners covering a range of computer literacy, interest in genetics, age, and sex. <b>Interventions:</b> Each doctor used the program in two consultations in which an actor played a woman concerned about her family history of cancer. Consultations were videotaped and followed by interviews with the video as a prompt to questioning. <b>Main outcome measures:</b> Use of computer program in the consultation. <b>Results:</b> The program was viewed as an appropriate application of information technology because of the complexity of cancer genetics and a sense of "guideline chaos" in primary care. Doctors found the program easy to use, but it often affected their control of the consultation. They needed to balance their desire to share the computer screen with the patient, driven by their concerns about the effect of the computer on doctor-patient communication, against the risk of premature disclosure of bad news. <b>Conclusions:</b> This computer program could provide the necessary support to assist assessment of genetic risk of cancer in primary care. The potential impact of computer software on the consultation should not be underestimated. This study highlights the need for careful evaluation when developing medical information systems. <h3>Key messages</h3> General practitioners are under increasing pressure to advise their patients about genetic predisposition to various diseases Computers could help doctors to give genetic advice by simplifying the construction and assessment of family trees and implementing referral guidelines This qualitative evaluation explored the context in which a computer program for assessing genetic risk of cancer would be used in general practice and issues surrounding its integration into a consultation Most of the doctors found the program easy to use, but it affected their control of the consultation—because of their desire to share the computer screen with the patient and their inability to anticipate the information that would be displayed The study identified important issues relating to the use of computers in consultations which may be of use in testing software for primary care in the future
An unorthodox approach to calculating sample size
Authors: S. Muller, S. L. Hider, T. Helliwell, C. D. Mallen
Journal: BMJ (2012)

Norman and colleagues raise an important issue—sample size calculations are at best an educated guess.1 While their suggestion might be helpful when an idea of sample size can be gleaned, in a recent study we had very little information at all.

The study was a primary care inception cohort of a rare and little researched condition. Initially, we …
Hepatic reticuloendothelial system cell iron deposition is associated with increased apoptosis in nonalcoholic fatty liver disease
Authors: Bryan D. Maliken, James E. Nelson, Heather M. Klintworth, Mary Beauchamp, Matthew M. Yeh, Kris V. Kowdley
Journal: Hepatology (2013)

The aim of this study was to examine the relationship between the presence of hepatic iron deposition, apoptosis, histologic features, and serum markers of oxidative stress (OS) and cell death in nonalcoholic fatty liver disease (NAFLD). Clinical, biochemical, metabolic, and independent histopathologic assessment was conducted in 83 unselected patients with biopsy-proven NAFLD from a single center. Apoptosis and necrosis in serum was quantified using serum cytokeratin 18 (CK18) M30 and M65 enzyme-linked immunosorbent assays and in liver by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining in situ . Serum malondialdehyde (MDA) and thioredoxin-1 (Trx1) levels were measured to evaluate OS. Presence of reticuloendothelial system (RES) cell iron in the liver was associated with nonalcoholic steatohepatitis ( P &lt; 0.05) and increased hepatic TUNEL staining ( P = 0.02), as well as increased serum levels of apoptosis-specific (M30; P = 0.013) and total (M65; P = 0.006) CK18 fragments, higher MDA ( P = 0.002) and lower antioxidant Trx1 levels ( P = 0.012), compared to patients without stainable hepatic iron. NAFLD patients with a hepatocellular (HC) iron staining pattern also had increased serum MDA ( P = 0.006), but not M30 CK18 levels or TUNEL staining, compared to subjects without stainable hepatic iron. Patients with iron deposition limited to hepatocytes had a lower proportion of apoptosis-specific M30 fragments relative to total M65 CK18 levels (37% versus ≤25%; P &lt; 0.05). Conclusions : Presence of iron in liver RES cells is associated with NASH, increased apoptosis, and increased OS. HC iron deposition in NAFLD is also associated with OS and may promote hepatocyte necrosis in this disease.
Fifteen children a day attend Scottish emergency departments as result of drinking alcohol
Authors: Bryan Christie
Journal: BMJ (2008)

A report from the Association of American Medical Colleges suggests that all 129 member medical schools should prohibit pharmaceutical and devices manufacturers from providing gifts, food, and travel to doctors, faculty members, and students.The report will be considered at the association's meeting in June.The association set up a task force to examine industry funding and to guide the association, medical schools, and teaching hospitals in developing policies and procedures about gifts and funding from industry.The report said that medical schools and teaching hospitals had become increasingly dependent on industry support for their core educational missions."This reliance raises concerns because such support, including gifts, can influence the objectivity and integrity of academic teaching, learning, and practice, thereby calling into question the commitment of academia and industry together to promote the public's interest by fostering the most cost-effective, evidencebased medical care possible."The report called on academic medical centers "to accelerate their adoption of policies that better manage, and when necessary, prohibit, academic-industry interactions that can inherently create conflicts of interest and undermine standards of professionalism."It concluded, "Industry should voluntarily discontinue those practices that compromise professionalism as well as public trust."The New York Times noted that medical schools, with their prominent professors and impressionable trainees, were particularly attractive targets for marketing (28 April; www.nytimes.com/
Poetry and Medicine
Authors: Barbara Seaman
Journal: JAMA (1990)

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Mutation analysis of the transcription factor PU.1 in younger adults (16 to 60 years) with acute myeloid leukemia: a study of the AML Study Group Ulm (AMLSG ULM)
Authors: Konstanze Döhner, Karen Tobis, Tobias Bischof, Stefan Hein, Richard F. Schlenk, Stefan Fröhling, Hartmut Döhner
Journal: Blood (2003)