tbuckley/cabot-search huggingface dataset:
THE LOCALIZATION IN ANIMALS OF BACTERIA ISOLATED FROM FOCI OF INFECTION
Authors: ALLEN C. NICKEL
Journal: JAMA (1926)

The rôle of bacteria, as found in various foci of infection, is extremely important. Although bacteria rarely enter the blood stream under normal conditions, they do harbor and thrive in various crypts, pockets or secluded spots in which there is imperfect drainage and which are therefore called foci. Occasionally, when conditions are suitable, the bacteria acquire enough virulence to invade other regions and then cause disease. Most observers who consider adequately all the facts agree that the bacteria as found in the various foci at times influence other parts of the same body in which they live. This view was voiced by Rush,<sup>1</sup>in 1801, who said, "I have been made happy by discovering that I have only added to the observations of other physicians, in pointing out a connection between the extracting of decayed and diseased teeth and the cure of general disease." Billings<sup>2</sup>has given us
Making Use of Clinical Audit: A Guide to Practice in the Health Professions
Authors: R. Baker
Journal: BMJ (1996)

Maurice Kogan, Sally Redfern Open University Press, pounds sterling14.99, pp 188 ISBN 0 335 19542 3

It might be tempting to conclude that the growing number of books on the subject is evidence of an increased acceptance of clinical audit in the daily work of health care professionals. However, this would be a mistake. The explanation is that, as audit is introduced throughout the NHS, it is gradually being encountered by different professional groups. When a group begins to undertake audit for the …
Alpha-Actinin 4 Is Associated with Cancer Cell Motility and Is a Potential Biomarker in Non–Small Cell Lung Cancer
Authors: Ming-Chuan Wang, Ying-Hua Chang, Chih-Chieh Wu, Yu-Chang Tyan, Hua-Chien Chang, Yih-Gang Goan, Wu-Wei Lai, Pin-Nan Cheng, Pao-Chi Liao
Journal: Journal of Thoracic Oncology (2014)
Total hip replacement using the Charnley prosthesis in inflammatory joint disease.
Authors: J Harris, S D Lightowler, R C Todd
Journal: Annals of the Rheumatic Diseases (1972)

steroids on any other patients than rheumatoids using this technique?DR.VERNON-ROBERTS We intended to carry out a further investigation on patients before and during therapy to evaluate them clinically by one of the recog- nized indices.We did not carry this out in the investigation presented, but Dr. Jessop made a clinical assessment of disease activity and we found a significant correlation between this and the phagocytic scores of macrophages in the untreated patients with rheumatoid arthritis, which gives us encouragement to continue this investigation.Regarding your second point, we had a few patients not included in this series who had polymyalgiarheumatica and were on steroids.They exhibited marked depression compared to our control group.DR. A. G. MOWAT (Oxford) These are two very nice papers, but I wonder if you have not confused yourselves by this simple 'skin window' technique?There are four or five stages to this inflammatory process: these include changes in the vessel wall, migration of cells through the vessel wall, chemotaxis of the cells, and finally phago- cytosis.Your method measures only phagocytosis.In rheumatoid arthritis there are important vascular changes and a serious defect in chemotaxis of the cells has been demonstrated (Mowat and Baum, 1971).DR.VERNON-ROBERTS We have qualified our state- ments and have made it clear that all these factors operate in inflammation.In using these techniques we cannot distinguish which aspects of the inflammatory response these compounds were inhibiting.We know, for example, that prednisolone inhibits every stage from the release of monocytes from the bone marrow pool to the phagocytic activity of the migrant cells.One does not know much about the mechanism of action of gold, but we are going to carry out further experiments on animals to study the production of monocytes, their emigration, chemotaxis, and so on.We think that the very significant difference between the rheumatoid and control groups and the results in our patients on gold and steroid therapy suggest that this relatively crude test may provide useful infor- mation on response to treatment.
α-synuclein induced synapse damage is enhanced by amyloid-β1-42
Authors: Clive Bate, Steve Gentleman, Alun Williams
Journal: Molecular Neurodegeneration (2010)

The pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB) is associated with the accumulation of aggregated forms of the α-synuclein (αSN) protein. An early event in the neuropathology of PD and DLB is the loss of synapses and a corresponding reduction in the level of synaptic proteins. However, the molecular mechanisms involved in synapse damage in these diseases are poorly understood. In this study the process of synapse damage was investigated by measuring the amount of synaptophysin, a pre-synaptic membrane protein essential for neurotransmission, in cultured neurons incubated with αSN, or with amyloid-β (Aβ) peptides that are thought to trigger synapse degeneration in Alzheimer's disease.We report that the addition of recombinant human αSN reduced the amount of synaptophysin in cultured cortical and hippocampal neurons indicative of synapse damage. αSN also reduced synaptic vesicle recycling, as measured by the uptake of the fluorescent dye FM1-43. These effects of αSN on synapses were modified by interactions with other proteins. Thus, the addition of βSN reduced the effects of αSN on synapses. In contrast, the addition of amyloid-β (Aβ)1-42 exacerbated the effects of αSN on synaptic vesicle recycling and synapse damage. Similarly, the addition of αSN increased synapse damage induced by Aβ1-42. However, this effect of αSN was selective as it did not affect synapse damage induced by the prion-derived peptide PrP82-146.These results are consistent with the hypothesis that oligomers of αSN trigger synapse damage in the brains of Parkinson's disease patients. Moreover, they suggest that the effect of αSN on synapses may be influenced by interactions with other peptides produced within the brain.
Renal Involvement in Organophosphate Poisoning-Reply
Authors: Ronald K. Albright
Journal: JAMA (1984)

In Reply.—  In addition to our initial report of possible Malathion nephrotoxicity, Wedin et al now report a case of poisoning with the organophosphate dimpylate, in which the renal manifestations were decreased urine output and crystalluria. The initial low urine output was probably related to volume depletion as opposed to any direct nephrotoxic effect from dimpylate.  The crystalluria is described as amorphous, and there is no mention of urine and serum chemistries or urine pH in the case report. Formation of crystals requires a supersaturated urinary solution with respect to a certain solute. There are no reports of organophosphates directly increasing the urinary excretion of calcium, uric acid, oxalate, or cystine to account for the crystalluria. The nicotinic manifestations of organophosphate poisoning do include muscular twitching and weakness, but frank rhabdomyolysis that might secondarily result in a large release of uric acid and uricosuria has not been reported. Calcium crystal
Management of cancer‐associated thrombotic microangiopathy: What is the right approach?
Authors: Theresa L. Werner, Neeraj Agarwal, Heather M. Carney, George M. Rodgers
Journal: American Journal of Hematology (2006)

Abstract A 49‐year‐old Caucasian woman presented with features suggestive of thrombotic microangiopathy (TMA). She did not respond to treatment with repeated plasma exchange and corticosteroids. A bone marrow biopsy revealed presence of metastatic carcinoma. A limited autopsy revealed presence of breast cancer with rib metastases. Though severe deficiency of von Willebrand factor‐cleaving protease was initially proposed as a key pathogenetic factor for thrombotic thrombocytopenic purpura, subsequent studies involving patients with cancer‐associated TMA did not find as severe a deficiency of von Willebrand factor‐cleaving protease as is seen in idiopathic cases of thrombotic thrombocytopenic purpura. Here we address one approach of management of these patients with cancer‐associated TMA. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
Diagnostic value of thyrotrophin releasing hormone tests in elderly patients with atrial fibrillation.
Authors: A B Davies, I Williams, R John, R Hall, M F Scanlon
Journal: BMJ (1985)

A prospective study was carried out to compare clinical and biochemical thyroid states with responses of thyroid stimulating hormone (TSH) to thyrotrophin releasing hormone (TRH) in elderly patients with either atrial fibrillation (n = 75; mean age (SD) 79.3 (6.0) years) or sinus rhythm (n = 73; mean age 78.4 (5.6) years) admitted consecutively to the department of geriatric medicine. No patient in either group had symptoms or signs of hyperthyroidism. Overall, the TSH responses to TRH did not differ significantly between the two groups. Ten (13%) of the patients with atrial fibrillation (of whom four had raised thyroid hormone concentrations) and five (7%) of the patients with sinus rhythm showed no TSH response to TRH while 26% of each group (20 and 19 patients, respectively) showed a much reduced response. Only one of 13 patients with apparently isolated atrial fibrillation showed no TSH response to TRH, and none of these 13 patients was hyperthyroid. In particular, three patients (two with atrial fibrillation and one with sinus rhythm) who showed no TSH response to TRH at presentation exhibited a return of TSH response to TRH at follow up six weeks later. In conclusion, reduced or absent TSH responses to TRH are common in sick elderly patients whether they have atrial fibrillation or sinus rhythm and whether they are euthyroid or hyperthyroid biochemically. An absence of response is therefore an uncertain marker of hyperthyroidism in these groups of patients, and diagnosis and ablative treatment should be based at least on the presence of raised circulating free triiodothyronine or free thyroxine concentrations, or both.
Some Points on THE ETIOLOGY, PROGNOSIS, AND TREATMENT OF GRAVES'S DISEASE
Authors: F. S. Langmead
Journal: BMJ (1929)

IT is irot my intention to attempt to deal fully w-ith the several aspects of Graves's disease, but ather to touch orr certain points in etiology, pronglosis, and treatment hich in my opinion are worthy of some consideration.The subject is one of wlhich our kniowledge is steadily growing, and about which there is much variation in opinion anid practice.This is as it should be, for there is plenlty of scope for trial and observatioin in many directions in this disorder at the present time, but little excuse for dogmatic assertions or rule-of-thumb proceduires. ETIOLOGY.A tenet which has materially delayed advanice in our ulnderstaniding of Graves's disease is that hiyperthyroidisrn is a sufficient explanation.The conception is a simple one, and suggests a sim)le remedy.If tire symptoms arid effects are due to hyperthyroidism, let us cripple the thvroid in some *w-ay or otlher, and n-ecessalrily the symptomlis must abate.Such a simllple conception, enitrenciihed as it is in the textbooks by the use of Graves's disease -anid hylperthyroidisnm as synonymous terms, we know now is untenable, an1d must be modified in various ways.Tire discovery and pr-eparation of a product of thyroi.dactivity thyro-iodia .orthyroxin-led to its beinig regarded as the peccanit substanice to excess of which tire symptoms are due, hut 'A1illiaminson and Pearsel have, shown1i t1hat distural)alice of the iodo-colloid ftunietioni ilas onlly ani iil(lire-ct relation to the thyro-toxicosis.These workers have denonstrated that the thyroid gland has two distiniet fulnctionial activities-one the production of tlryro-iodin, the other of a secretion- and tirat it is this latter which is directly elated to the
Isotretinoin treatment for acne vulgaris and its cutaneous and ocular side-effects
Authors: R.M. Azurdia, G.R. Sharpe
Journal: British Journal of Dermatology (1999)

Journal Article Isotretinoin treatment for acne vulgaris and its cutaneous and ocular side‐effects Get access R.M. Azurdia, R.M. Azurdia Department of Dermatology, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, U.K. Search for other works by this author on: Oxford Academic Google Scholar G.R. Sharpe G.R. Sharpe Department of Dermatology, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 141, Issue 5, 1 November 1999, Page 947, https://doi.org/10.1046/j.1365-2133.1999.03188.x Published: 01 November 1999
Factors determining the loss of ductus arteriosus responsiveness to prostaglandin E.
Authors: R I Clyman, F Mauray, C Roman, M A Heymann, B Payne
Journal: Circulation (1983)

The ductus arteriosus of the newborn infant varies in its ability to dilate when doses of prostaglandin E (PGE) are administered. We infused PGE2 into 15 late-gestation newborn lambs to determine which factors regulate the ability of the ductus arteriosus to respond to PGE. PGE2 dilated the ductus in 10 lambs (responders); in five other lambs, despite similar PGE2 concentrations, there was no effect (nonresponders). The measured ductus resistance after the PGE2 infusion was directly related to the ductus resistance before the infusion. Responders had a larger left-to-right shunt through the ductus before the PGE infusion than nonresponders. Ductus that were isolated and studied in vitro from lambs that were nonresponsive to PGE2 (in vivo) were limited in their ability to relax with PGE2 as well as to actively contract with oxygen and indomethacin. This generalized loss of ductus responsiveness was directly related to the amount of the left-to-right shunt through the lumen of the ductus. These observations are consistent with the hypothesis that the constriction of the ductus arteriosus after birth limits the ability of the ductus to respond to PGE therapy.
Inducible nitric oxide synthase (iNOS) liver expression and nitrotyrosine (NTY) accumulation in primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH)
Authors: Paloma Sanz-Cameno, Carmelo Garcia-Monzon, Pedro L. Majano, Luisa Garcia-Buey, M.Jesus Borque, Asuncion Garcia-Sanchez, Ricardo Moreno-Otero
Journal: Journal of Hepatology (2001)
Designer receptors: therapeutic adjuncts to cell replacement therapy in Parkinson’s disease
Authors: Elena M. Vazey, Gary Aston-Jones
Journal: Journal of Clinical Investigation (2014)

Cell replacement for restoring neuronal populations in Parkinson’s disease has been demonstrated as a potential therapeutic strategy over several decades of studies; however, a number of issues regarding sources of replacement neurons and optimization of therapeutic efficacy in vivo have hampered clinical implementation. In this issue of the JCI, Dell’Anno and colleagues evaluated the use of induced dopaminergic (iDA) neurons that were generated by direct fibroblast reprogramming for transplantation and demonstrated that postmitotic iDA neurons stably and functionally integrate into host striatum to produce motor improvements in 6-OHDA rats, a Parkinson’s disease model. Furthermore, using designer receptors exclusively activated by designer drugs (DREADDs) in iDA grafts to noninvasively increase dopamine release from grafted neurons, the authors were able to remotely control transplanted neurons and enhance therapeutic efficacy. This initial proof-of-concept study is the first application of DREADD technology to treat neurodegenerative dysfunction, and by using DREADDs as an adjunct to iDA cell therapy, it presents a novel strategy to overcome some current caveats of cell replacement therapy.
<i>SMAD4</i> Gene Mutations Are Associated with Poor Prognosis in Pancreatic Cancer
Authors: Amanda Blackford, Oscar K. Serrano, Christopher L. Wolfgang, Giovanni Parmigiani, Siân Jones, Xiaosong Zhang, D. Williams Parsons, Jimmy Cheng-Ho Lin, Rebecca J. Leary, James R. Eshleman, Michael Goggins, Elizabeth M. Jaffee, Christine A. Iacobuzio-Donahue, Anirban Maitra, John L. Cameron, Kelly Olino, Richard Schulick, Jordan Winter, Joseph M. Herman, Daniel Laheru, Alison P. Klein, Bert Vogelstein, Kenneth W. Kinzler, Victor E. Velculescu, Ralph H. Hruban
Journal: Clinical Cancer Research (2009)

Recently, the majority of protein coding genes were sequenced in a collection of pancreatic cancers, providing an unprecedented opportunity to identify genetic markers of prognosis for patients with adenocarcinoma of the pancreas.We previously sequenced more than 750 million base pairs of DNA from 23,219 transcripts in a series of 24 adenocarcinomas of the pancreas. In addition, 39 genes that were mutated in more than one of these 24 cancers were sequenced in a separate panel of 90 well-characterized adenocarcinomas of the pancreas. Of these 114 patients, 89 underwent pancreaticoduodenectomy, and the somatic mutations in these cancers were correlated with patient outcome.When adjusted for age, lymph node status, margin status, and tumor size, SMAD4 gene inactivation was significantly associated with shorter overall survival (hazard ratio, 1.92; 95% confidence interval, 1.20-3.05; P = 0.006). Patients with SMAD4 gene inactivation survived a median of 11.5 months, compared with 14.2 months for patients without SMAD4 inactivation. By contrast, mutations in CDKN2A or TP53 or the presence of multiple (> or =4) mutations or homozygous deletions among the 39 most frequently mutated genes were not associated with survival.SMAD4 gene inactivation is associated with poorer prognosis in patients with surgically resected adenocarcinoma of the pancreas.
The Hemodynamic and Metabolic Interrelationships in the Activity of Epinephrine, Norepinephrine and the Thyroid Hormones
Authors: WILLIAM R. BREWSTER, JAMES P. ISAACS, PATRICIA F. OSGOOD, THELMA L. KING
Journal: Circulation (1956)

The hemodynamic and metabolic effects of a total sympathetic block and of the infusion of l -epinephrine or l -norepinephrine were studied in 27 euthyroid dogs and in 31 thyroid-fed dogs. The physiologic changes produced by increased concentrations of the thyroid hormones were abolished by preventing the reflex release of epinephrine and norepinephrine with a total sympathetic block. The inotropic, chronotropic and calorigenic effects of l -epinephrine and of l -norepinephrine were found to be increased by thyroid feeding. It is concluded that there is a dynamic interrelationship between the thyroid hormones and those of the adrenal medulla and sympathetic nerve endings. The hemodynamic and metabolic changes of thyrotoxicosis are not the result of the isolated activity of the thyroid hormones, but rather are due to the physiologic effects of epinephrine and norepinephrine, as augmented by the thyroid hormones. Studies indicate that l -norepinephrine is the predominant mediator of the changes produced by thyroid feeding.
AN ANTIVIRAL SUBSTANCE FROM PENICILLIUM FUNICULOSUM
Authors: Richard E. Shope
Journal: The Journal of Experimental Medicine (1966)

1. Helenine prevents the establishment in mice of passive viral immunity by anti-Semliki serum of swine, rabbit, or guinea pig origin. 2. A period of 12 days must elapse, between the antiviral serum administration and challenge with virus, for prevention of the establishment of passive immunity to become apparent. This period is believed to correspond to that in which injected antibody persists in circulation in the injected host. 3. Helenine is effective in preventing the establishment of passive viral immunity by heterologous antiviral sera when it is administered any time during a period of 6 days, extending from 4 days before to 2 days after injection of the antiviral serum. 4. Helenine does not prevent the establishment of passive viral immunity by antiviral sera of mouse origin (homologous). 5. Evidence is presented to indicate that the phenomenon of the prevention of the establishment of passive viral immunity by heterologous antiviral sera is not effected directly, but rather is mediated through some substance that helenine induces the injected host to elaborate. 6. The capacity to prevent the establishment of passive viral immunity could not be exhausted by repeated preceding injections of helenine at 2- or 3-day intervals. 7. Evidence is presented to indicate that the helenine-induced material does not act upon antiviral antibody per se but rather on heterologous foreign protein that happens to be labeled as Semliki Forest virus antibody. This helenine-induced material, whatever its nature, appears to enhance the capacity of the injected host to recognize and dispose of foreign protein. 8. Statolon, a material that like helenine is a known inducer of interferon, is, like helenine, also capable of preventing the establishment of passive viral immunity by heterologous antiviral sera. 9. Experiments designed to determine whether the induced material responsible for the antipassive immunity effect of helenine is interferon have yielded inconclusive answers thus far.
Angiotensin II type 1 receptor blockade to control blood pressure in postmenopausal women: Influence of hormone replacement therapy
Authors: Francisco Fernández-Vega, José Abellán, Onofre Vegazo, Soledad García De Vinuesa, José Carlos Rodríguez, Benito Maceira, Saturnino Sanz De Castro, Roberto Robles Nicolás, José Luño
Journal: Kidney International (2002)
The complex facts of taste
Authors: A. W. Logue
Journal: Behavioral and Brain Sciences (2008)

Abstract There is both empirical evidence that supports, and does not support, the four basic tastes, as well as the labeled-line and across-fiber pattern theories. All of these concepts have proven useful to researchers investigating taste coding, and should be appreciated for their heuristic value. Dismissal of any of them is neither supported by evidence nor productive.
What is a factorial study design?
Authors: P. Sedgwick
Journal: BMJ (2014)

Researchers investigated whether inclusion of glutamine or selenium in a standard isonitrogenous, isocaloric preparation of parenteral nutrition affected the occurrence of new infections in critically ill patients. A randomised double blind placebo controlled trial was conducted, using a full factorial study design. There were two factors—treatment with glutamine (20.2 g/day) or glutamine placebo and treatment with selenium (500 μg/day) or selenium placebo, each for up to seven days. Participants were 502 adults in intensive care units or high dependency units who had gastrointestinal failure and required parenteral nutrition.1

The outcome measure was a new clinically suspected infection within the first 14 days of treatment. The trial found no evidence of an interaction between glutamine and selenium in treatment effect (P=0.96). Selenium supplementation had no significant effect on the development of new infections (odds ratio 0.81, 95% confidence interval 0.57 to 1.15). Glutamine also had no significant effect on the development of new infections (odds ratio 1.07, 0.75 to 1.53). It was concluded that the supplementation of parenteral nutrition with glutamine or selenium had no effect on the development of new infections in critically ill patients.

Which of the following statements, if any, are true?

Statements a , b , c, and d are all true.

The aim of the trial was to investigate whether inclusion of glutamine or selenium in parenteral nutrition had an effect on the development of new infections in critically ill patients. A randomised double …