tbuckley/cabot-search huggingface dataset:
Acceptable Risk and Practical Safety
Authors: William J. Darby
Journal: JAMA (1973)

Some of the broad food production issues are ignored by many who zealously advocate everincreasing constraints on food production and processing technology without appreciation of their broader impact upon the health and wellbeing of mankind. I examine these issues as well as certain aspects of the decision-making process, first, however, identifying some of the hazards that exist and then considering the responsibility of scientists and others within this framework. Only from such a perspective can objective, rational, nonemotional, informed judgments emerge that properly relate risks and benefits so that man enjoys the maximum betterment of health and quality of life attainable from a full appreciation of science and technology. Value judgments that determine policy decisions and regulatory actions are not exclusively scientific. However, the perspective from which they are drawn must reflect the multifaceted surfaces of scientific information and advances without exaggeration or distortion. <h3>World Food Risks</h3> The major masses
DO GENDER DIFFERENCES IN ATHEROSCLEROTIC PLAQUE COMPOSITION PERSIST WITH AGING? A QUANTITATIVE NON INVASIVE ASSESSMENT BY CORONARY CT ANGIOGRAPHY
Authors: Ali Masud, Gudrun Feuchtner, Daniel Jodocy, Guy Friedrich, Roger S. Blumenthal, Matthew J.J. Budoff, Khurram Nasir
Journal: Journal of the American College of Cardiology (2010)
Impaired cell mediated immunity in haemophilia in the absence of infection with human immunodeficiency virus.
Authors: R Madhok, A Gracie, G D Lowe, A Burnett, K Froebel, E Follett, C D Forbes
Journal: BMJ (1986)

The cell mediated immune response was evaluated in vivo in 29 patients with clinically severe haemophilia by means of the dinitrochlorobenzene skin test. All patients had a response below the median normal value, and in 19 the response was on or below the lower limit of the normal range. There was no difference in skin response between patients positive and negative for the human immunodeficiency virus (HIV; formerly known as human T cell lymphotropic virus III or lymphadenopathy associated virus). In the whole group, and in seronegative patients (n = 17), there was an inverse relation between exposure to clotting factor and skin response. In seropositive patients (n = 12) no such association was apparent. This study shows that clotting factor concentrate impairs the cell mediated immune response to a new antigen in the absence of infection with HIV.
Book: The Rise and Fall of Modern Medicine
Authors: J. P Bunker
Journal: BMJ (1999)

James Le Fanu Little Brown, £20, pp 490 ISBN 0 316 64836 1 Rating: ![Graphic][1]</img> ![Graphic][2]</img> ![Graphic][3]</img> James Le Fanu tells us that medicine today is dull, which, from his perspective in general practice, it may have become. Whether medicine has lost the excitement that accompanied the explosion in treatments in the past 50 years, as he contends, medicine has certainly changed beyond recognition. He leads us instructively through these years of medical change. In the first of four “paradoxes” with which he introduces and later closes his book, Le Fanu writes: “Medicine is, sadly, no longer as satisfying as in the past. Many of the most interesting diseases that tested the doctor's clinical acumen have simply disappeared, and the family doctor is lucky to see a patient with a serious acute medical problem from one week to the next.” As a result of past success in prevention and treatment, the primary care doctor is left with the symptomatic care of patients suffering from chronic illnesses and of counselling the “worried well.” Serious illness, acute as well as chronic, has increasingly become the province of hospital based physicians and surgeons. In his second paradox Le Fanu writes: “It is most peculiar that as medicine has become more successful, the proportion of the public who apparently are ‘worried well’ about their health has increased.” As a consequence of epidemiological evidence that an individual's life style can affect his or her health, “an excessive concern about ‘health’ can … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Insulin-like growth factor binding protein-1 (IGFBP-1): a multifunctional role in the human female reproductive tract
Authors: D. J. Fowler
Journal: Human Reproduction Update (2000)

Insulin-like growth factor-1 (IGFBP-1) is particularly important in human female reproductive physiology, where it is involved with other factors in a complex system which regulates menstrual cycles, puberty, ovulation, decidualization, implantation and fetal growth. This has implications for clinical obstetrics and gynaecology, where there is evidence for a pathophysiological role for IGFBP-1 in pre-eclampsia, intrauterine growth restriction, polycystic ovarian syndrome and trophoblast and endometrial neoplasms.
The Heartbreak of Psoriasis
Authors: Richard B. Stoughton
Journal: JAMA (1974)

IT is unfortunate that commercials on radio, television, in newspapers, and elsewhere portray mild scaling of the scalp or skin as "the heartbreak of psoriasis." Many individuals with mild dryness of their skin or ordinary dandruff immediately begin to worry that they may have psoriasis, a fear that may not be dispelled easily. Also, patients with psoriasis eagerly purchase each new product in hope of helping their disease. These advertised formulations are quite bland and<i>have very little, if any, beneficial effect in controlling the lesions of psoriasis.</i> The reasons for these commercials are quite obvious. They are profitable to the manufacturer and the advertising media. However, it is probable that more harm than good comes from this approach to treating patients with psoriasis. Psoriasis is a common but complicated disease that is not amenable to control by over-the-counter or through-the-tube preparations. In fact, detailed regimens worked out on a
Linking brain to mind in normal behavior and schizophrenia
Authors: Stephen Grossberg
Journal: Behavioral and Brain Sciences (2003)

Abstract To understand schizophrenia, a linking hypothesis is needed that shows how brain mechanisms lead to behavioral functions in normals, and also how breakdowns in these mechanisms lead to behavioral symptoms of schizophrenia. Such a linking hypothesis is now available that complements the discussion offered by Phillips &amp; Silverstein (P&amp;S).
The PapG-adhesin at the tip of P-fimbriae provides Escherichia coli with a competitive edge in experimental bladder infections of cynomolgus monkeys.
Authors: J Winberg, R Möllby, J Bergström, K A Karlsson, I Leonardsson, M A Milh, S Teneberg, D Haslam, B I Marklund, S Normark
Journal: The Journal of Experimental Medicine (1995)

Human urinary tract infection is an infectious disease that depends on a series of host-microbial interactions. The bacteria first colonize the colon and then the periurethral/vaginal areas; they ascend to and infect first the bladder and then the kidneys. Expression of Escherichia coli P-fimbriae constitutes the strongest correlation to renal pathogenicity, but is also related to first-time cystitis in children. The role of P-fimbriae in the preceding steps in the infectious process is unknown. To examine this, we constructed, from a P-fimbriated E. coli strain with a class II G-adhesin preferentially binding to globoside, one isogenic mutant lacking the G-adhesin and another isogenic mutant in which we replaced the papG class II allele with a class III adhesin preferentially binding to the Forssman antigen. We report here the comparison of the adhesin knockout mutant (DS17-8) and the class-switch mutant (DS17-1) with the wild-type (DS17) for in vivo colonization of the gut, vagina, and bladder of cynomolgus monkeys. It was recently shown that the class II tip G-adhesin is a prerequisite for acute pyelonephritis to occur in the monkey model in the absence of other kidney-specific adhesins or obstruction of the urinary flow. Here we show that it is not required for bladder infection but gives a competitive advantage in mixed infections. In the vagina and colon, the G-adhesin gives no competitive advantage.
Seasonal changes in human hair growth
Authors: VALERIE A. RANDALL, F. J. G. EBLING
Journal: British Journal of Dermatology (1991)

Various parameters of hair growth were determined every 28 days for 18 months in 14 healthy Caucasian men aged 18–39 with indoor occupations in Sheffield, U. K. (latitude 53.4°N). In the scalp the proportion of follicles in anagen reached a single peak of over 90% in March, and fell steadily to a trough in September. The number of shed hairs reached a peak around August/September, when least follicles were in anagen. At this time the average loss of hairs was about 60 per day, more than double that during the preceding winter. The rate of growth of the beard was lowest in January and February and increased steadily from March to July to reach a peak about 60% above the winter level. The rate of growth of thigh hair showed a similar pattern though with less pronounced differences. No seasonal fluctuations in finger- or toenail growth were detected.
The water method significantly enhances patient-centered outcomes in sedated and unsedated colonoscopy
Authors: F. Leung, J. Leung, S. Mann, S. Friedland, F. Ramirez
Journal: Endoscopy (2011)

Failure of cecal intubation when using air insufflation during scheduled unsedated colonoscopy in veterans prompted a literature search for a less uncomfortable approach. Water-related maneuvers as “adjuncts” to air insufflation were identified as effective in minimizing discomfort, although medication requirement was not reduced and willingness to repeat unsedated colonoscopy was not addressed. These adjunct maneuvers were combined with turning the air pump off to avoid colon elongation during insertion. Warm water infusion in lieu of air insufflation was evaluated in observational studies. Subsequent refinements evolved into the water method – a combination of air exclusion by aspiration of residual air to minimize angulations at flexures and a dynamic process of water exchange to remove feces in order to clear the view and aid insertion. In subsequent randomized controlled trials, the water method significantly reduced medication requirement, increased the proportion of patients in whom complete unsedated colonoscopy could be achieved, reduced patient recovery time burdens (sedation on demand), decreased abdominal discomfort during and after colonoscopy, enhanced cecal intubation, and increased willingness to repeat the procedure (scheduled unsedated). Supervised education of trainees and self-learning by an experienced colonoscopist were feasible. Lessons learned in developing the water method for optimizing patient-centered outcomes are presented. These proof-of-principle observations merit further research assessment in diverse settings.
Fibrosing alveolitis with autoimmune haemolytic anaemia: two case reports.
Authors: J W Scadding
Journal: Thorax (1977)

<b>Objective: </b> To examine the contribution of neuropsychological test performance to treatment decision-making capacity in community volunteers with mild to moderate dementia. <b>Methods: </b> The authors recruited volunteers (44 men, 44 women) with mild to moderate dementia from the community. Subjects completed a battery of 11 neuropsychological tests that assessed auditory and visual attention, logical memory, language, and executive function. To measure decision making capacity, the authors administered the Capacity to Consent to Treatment Interview, the Hopemont Capacity Assessment Interview, and the MacCarthur Competence Assessment Tool—Treatment. Each of these instruments individually scores four decisional abilities serving capacity: understanding, appreciation, reasoning, and expression of choice. The authors used principal components analysis to generate component scores for each ability across instruments, and to extract principal components for neuropsychological performance. <b>Results: </b> Multiple linear regression analyses demonstrated that neuropsychological performance significantly predicted all four abilities. Specifically, it predicted 77.8% of the common variance for understanding, 39.4% for reasoning, 24.6% for appreciation, and 10.2% for expression of choice. Except for reasoning and appreciation, neuropsychological predictor (β) profiles were unique for each ability. <b>Conclusions: </b> Neuropsychological performance substantially and differentially predicted capacity for treatment decisions in individuals with mild to moderate dementia. Relationships between elemental cognitive function and decisional capacity may differ in individuals whose decisional capacity is impaired by other disorders, such as mental illness.
Parathyroid cell proliferation in normal and chronic renal failure rats. The effects of calcium, phosphate, and vitamin D.
Authors: T Naveh-Many, R Rahamimov, N Livni, J Silver
Journal: Journal of Clinical Investigation (1995)

Secondary hyperparathyroidism is characterized by an increase in parathyroid (PT) cell number, and parathyroid hormone (PTH) synthesis and secretion. It is still unknown as to what stimuli regulate PT cell proliferation and how they do this. We have studied rats with dietary-induced secondary hyper- and hypoparathyroidism, rats given 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and rats after 5/6 nephrectomy for the presence of PT cell proliferation and apoptosis. PT cell proliferation has been measured by staining for proliferating cell nuclear antigen (PCNA) and apoptosis by in situ detection of nuclear DNA fragmentation and correlated with serum biochemistry and PTH mRNA levels. A low calcium diet led to increased levels of PTH mRNA and a 10-fold increase in PT cell proliferation. A low phosphate diet led to decreased levels of PTH mRNA and the complete absence of PT cell proliferation. 1,25 (OH)2D3 (25 pmol/d x 3) led to a decrease in PTH mRNA levels and unlike the hypophosphatemic rats there was no decrease in cell proliferation. There were no cells undergoing apoptosis in any of the experimental conditions. The secondary hyperparathyroidism of 5/6 nephrectomized rats was characterized by an increase in PTH mRNA levels and PT cell proliferation which were both markedly decreased by a low phosphate diet. The number of PCNA positive cells was increased by a high phosphate diet. Therefore hypocalcemia, hyperphosphatemia and uremia lead to PT cell proliferation, and hypophosphatemia completely abolishes this effect. Injected 1,25 (OH)2D3 had no effect. These findings emphasize the importance of a normal phosphate and calcium in the prevention of PT cell hyperplasia.
152 TRANSDERMAL RIVASTIGMINE FOR TREATMENT OF ENCEPHALOPATHY IN LIVER CIRRHOSIS – A RANDOMIZED PLACEBO CONTROLLED TRIAL (TREC TRIAL)
Authors: P. Basu, N.J. Shah, N. Krishnaswamy, H. Hampole, T. Pacana, K. Rayapudi, R. Brown
Journal: Journal of Hepatology (2010)
Alcohol and kidney damage: a Janus-faced relationship
Authors: Elke Schaeffner, Eberhard Ritz
Journal: Kidney International (2012)

It has been known for a long time that excessive consumption of alcohol has adverse effects, including adverse impact on kidneys and kidney disease. Recently, observational evidence has been provided that moderate alcohol consumption is associated with less cardiovascular and renal risk. These issues had been summarized and discussed at the recent congress of the European Society for Biomedical Research and Alcoholism in Vienna.
Letter: Poisoned children.
Authors: J R Sibert
Journal: BMJ (1974)

concentration of the dialysate still gave a negative result.This woman clearly had a massive over- dose of tricyclic antidepressants and it was considered that her chances of survival were extremely poor.It seemed to us that haemo- dialysis was responsible for a dramatic clinical improvement.This does not seem to be supported by the analyses for the drug we were alble to make.In fact the decrease in plasma imipramine level did not approach the half-time of 3hours reported by Ciba-Geigy (N.Z.) Ltd. (personal com- munication).From our results no increase in the rate of fail of plasma imipramine occurred during dialysis.Unfortunately the lack of samples prior to dialysis leaves some doubt on this point.Our inability to locate any imiprarnine in the dialysate may be explained by the interesting comments of Drs.Asbach and Schuiler (24 August, p. 524) who claim that imirpramine is taken up by the polyvinyl chloride of the extracorporeal blood-line system.Our limited eWerience, that of Harthorne et al.3 and the recent letters from Drs. Asbach and Schuiler have encouraged us to give early consideration to this form of treatment in patients with severe poisoning.However, the recovery of significant amounts of drug by forced diuresis may yet indicate that this method is the most suitable way of eliminating absorbed imipramine and other tricydlic antidepressants.-Weare, etc.,
Comparative Effectiveness of Shock Wave Lithotripsy and Ureteroscopy for Treating Patients With Kidney Stones
Authors: Charles D. Scales, Julie C. Lai, Andrew W. Dick, Jan M. Hanley, Jeroen van Meijgaard, Claude M. Setodji, Christopher S. Saigal
Journal: JAMA Surgery (2014)

Shock wave lithotripsy (SWL) and ureteroscopy (URS) account for more than 90% of procedural interventions for kidney stones, which affect 1 in 11 persons in the United States. Efficacy data for SWL are more than 20 years old. Advances in URS, along with emerging evidence of reduced efficacy of modern lithotripters, have created uncertainty regarding the comparative effectiveness of these 2 treatment options.To compare the effectiveness of SWL and URS to fragment or remove urinary stones in a large private payer cohort.We performed a retrospective cohort study of privately insured beneficiaries who had an emergency department visit for a kidney stone and subsequently underwent SWL or URS. Using an instrumental variable approach to control for observed and unobserved differences between the 2 groups, we created a bivariate probit model to estimate the probability of repeat intervention following an initial procedure.A second procedure (SWL or URS) within 120 days of an initial intervention to fragment or remove or a kidney stone.Following an acute care visit for a kidney stone, 21 937 patients (45.8%) underwent SWL and 25 914 patients (54.2%) underwent URS to fragment or remove the stone. After the initial URS, 4852 patients (18.7%) underwent an additional fragmentation or removal procedure compared with 5186 patients (23.6%) after the initial SWL (P < .001). After adjusting for observed and unobserved variables, the estimated probabilities of repeat intervention were 11.0%(95%CI, 10.9-11.1) following SWL and 0.3%(95%CI, 0.325-0.329) following URS.Among privately insured beneficiaries requiring procedural intervention to remove a symptomatic stone, repeat intervention is more likely following SWL. For the marginal patient (as opposed to the average patient), the probability of repeat intervention is substantially higher.
Dose Optimization for Long-term rAAV-mediated RNA Interference in the Nigrostriatal Projection Neurons
Authors: Ayse Ulusoy, Gurdal Sahin, Tomas Björklund, Patrick Aebischer, Deniz Kirik
Journal: Molecular Therapy (2009)

Short-hairpin RNA (shRNA)-mediated gene knockdown is a powerful tool for targeted gene silencing and an emerging novel therapeutic strategy. Recent publications, however, reported unexpected toxicity after utilizing viral-mediated shRNA knockdown in vivo. Thus, it is currently unclear whether shRNA-mediated knockdown strategy can be used as a safe and efficient tool for gene silencing. In this study, we have generated rAAV vectors expressing shRNAs targeting the rat tyrosine hydroxylase (TH) mRNA (shTH) for testing the efficacy of in vivo TH knockdown in the nigral dopaminergic neurons. At high titers, not only the shTH vectors but also the scrambled and green fluorescence protein (GFP)-only controls caused cell death. In a dose-response study, we identified a dose window leading to >60% decrease in TH(+) neurons without any change in vesicular monoamine transporter-2 (VMAT2) expression. Moreover, using the safe and efficient dose, we showed that dopamine (DA) synthesis rate was significantly reduced and this lead to emergence of motor deficits in the shTH-expressing rats. Interestingly, these animals showed very robust and long-lasting recovery after a single systemic L-3,4-dihydroxyphenylalanine (L-DOPA) administration beyond what can be achieved in 6-hydroxydopamine (6-OHDA)-lesioned rats. Our results have implications for both mechanistic and therapeutic studies utilizing long-term shRNA-mediated gene silencing in the nigrostriatal projection system.
Efficacy of Post-Operative Clopidogrel Treatment in Patients Revascularized With Coronary Artery Bypass Grafting After Myocardial Infarction
Authors: Rikke Sørensen, Steen Z. Abildstrøm, Peter R. Hansen, Anders Hvelplund, Charlotte Andersson, Mette Charlot, Emil L. Fosbøl, Lars Køber, Jan K. Madsen, Gunnar H. Gislason, Christian Torp-Pedersen
Journal: Journal of the American College of Cardiology (2011)
Justice and allocation of medical resources.
Authors: R Gillon
Journal: BMJ (1985)

In one of a series of short articles on philosophical medical ethics, Gillon examines the principle of justice as it applies to adjudicating competing claims for the distribution of scarce medical resources. He describes Aristotle's theory of justice--with its demands of formal equity, impartiality, and fairness--and then considers various substantive criteria that have been proposed to justify choosing among competing candidates for scarce resources. In the absence of an acceptable way to give consistent moral priority to any of the criteria, he concludes, practical systems should be set up to resolve conflicts by taking into account the fundamental moral values of respect for autonomy, beneficence, and nonmaleficence while incorporating Aristotle's formal principle of justice.
On the Uptake of Materials by the Intact Liver THE CONCENTRATIVE TRANSPORT OF RUBIDIUM-86
Authors: Carl A. Goresky, Glen G. Bach, Brita E. Nadeau
Journal: Journal of Clinical Investigation (1973)

In this study we use the multiple indicator dilution technique to outline the kinetic mechanisms underlying the uptake of rubidium, a cation which, in the steady state, is concentrated by hepatic parenchymal cells. We inject a mixture of 51Cr-labeled red blood cells (a vascular reference substance), 22Na (which is confined to the extracellular space, the expected extravascular distribution space for rubidium, in the absence of cellular uptake), and 86Rb into the portal vein and obtain normalized outflow patterns, expressed as outflowing fractions of each injected mass per milliliter vs. time. The labeled red cell curve rises to the highest and earliest peak and decays rapidly. That for labeled sodium rises to a later and lower peak, and decays less rapidly. Its extrapolated recovery is equal to that for the red cells. The observed 86Rb curve consists of two parts: an early clearly defined peak of reduced area, related to the 22Na peak in timing; and a later tailing, obscured by recirculation, so that total outflow recovery cannot be defined (even though it would be expected to be the same). We model the concentrative uptake of 86Rb and find two corresponding outflow fractions: throughput material, which sweeps past the cell surface as a wave delayed with respect to the vascular reference (tracer which has not entered cells); and exchanging material (tracer which has entered cells and later returns to the circulation). We find that the outflow form of the rubidium curve, the presence of both a relatively clearly defined throughput component and a relatively prolonged low-in-magnitude tailing, is consequent to the concentrative character of the transport mechanism, to the presence of an influx rate constant many times the efflux rate constant. The modeling which we develop is general, and has potential application in situations where transport is nonconcentrative.