tbuckley/cabot-search huggingface dataset:
Drugs for dementia should receive accelerated approval, says world envoy
Authors: M. Limb
Journal: BMJ (2014)

<h3>Abstract</h3> In many developing and regenerating systems, tissue pattern is established through gradients of informative morphogens, but we know little about how cells interpret these. Using experimental manipulation of early chick embryos including misexpression of an inducer (VG1 or ACTIVIN) and an inhibitor (BMP4), we test two alternative models for their ability to explain how the site of primitive streak formation is positioned relative to the rest of the embryo. In one model, cells read morphogen concentrations cell-autonomously. In the other, cells sense changes in morphogen status relative to their neighbourhood. We find that only the latter model can account for the experimental results, including some counter-intuitive predictions. This mechanism (which we name “neighbourhood watch” model) illuminates the classic “French Flag Problem” and how positional information is interpreted by a sheet of cells in a large developing system. <h3>Summary statement</h3> In a large developing system, the chick embryo before gastrulation, cells interpret gradients of positional signals relative to their neighbours to position the primitive streak, establishing bilateral symmetry.
Inhibit GSK-3β or there’s heartbreak dead ahead
Authors: Elizabeth Murphy
Journal: Journal of Clinical Investigation (2004)

Numerous signaling pathways have been shown to mediate cardioprotection, but the end effectors that mediate protection are only beginning to be elucidated. Numerous cardioprotective drugs are shown to converge on glycogen synthase kinase-3β (GSK-3β) . The phosphorylation and inhibition of GSK-3β lead to inhibition or delayed activation of the mitochondrial permeability transition, a key regulator of apoptosis.
Letter: Occult abdominal injury.
Authors: B J Pardy
Journal: BMJ (1976)

others,3 emphasise the need for a standard- ised stimulus and a standardised means of measuring the dermographic response.Only with standardised testing procedures can we estimate with confidence (a) the incidence of dermographism among patients and nonpatients and (b) the relationship between dermographism and other cutaneous responses (for example, chronic urticaria and hyper- reactivity to intradermal allergy testing).)
Family unit in a children's psychiatric hospital.
Authors: M Lynch, D Steinberg, C Ounsted
Journal: BMJ (1975)

The need for effective management of disorders of parent/child relationships is repeatedly stressed. Despite the bulk of theoretical work on the subject there is little information on the practical management of the clinical problems that arise. We describe a unit designed and staffed for the management of such disorders. In our view it meets a need in a way that could be difficult or impossible for most paediatric, psychiatric, and social services as they are at present organized.
PTU-252 CA19.9—are we using it appropriately and is it cost effective?
Authors: R K Felwick, R Olufadi, S Bridger
Journal: Gut (2012)

<h3>Introduction</h3> CA19.9 is frequently used in the assessment of patients with suspected pancreatic cancer or cholangiocarcinoma. Although specific guidelines are not available, data suggests that it should not be used for screening and only used in conjunction with appropriate imaging. The aim of this study was to investigate the clinical utility and cost effectiveness of using CA19.9 as a marker for pancreatic cancer and cholangiocarcinoma in a district general hospital. <h3>Methods</h3> A retrospective analysis was undertaken of all patients with a CA19.9 measurement over a period of 12 months. Data on liver biochemistry and abdominal imaging were collected. The results were compared to identify those patients in whom; (i) a positive CA19.9 result was associated with the presence of biliary or pancreatic malignancy (ii) those patients in whom CA19.9 was inappropriately requested. A cost analysis was undertaken. <h3>Results</h3> 492 CA19.9 assays were performed in 12 months. 245 were in patients who had not had abdominal imaging or LFTs measured. 247/492 had both imaging and LFTs and were included in the initial analysis. 102/247 had a positive CA19.9. A total of 45/247 were found to have a pancreatic or bilary malignancy 38/45 had a positive CA19.9. This was negative in 7/45. The overall clinical utility of CA19.9 was poor. From the 492 assays performed during the year a positive CA19.9 was associated with a new malignancy in just 7% (38/492). Overall 63% of patients with a positive CA19.9 did not have pancreatic cancer (PPV 37%) Conversely 5% of those with a negative result did (95% NPV). 22% of patients with pancreatic malignancy had normal LFTs at the time of diagnosis. In total 103/492 (20%) of assays were duplicates. Only 36/103 (35%) were in patients with confirmed malignancy. 67 assays were requested in patients with normal abdominal imaging or in the absence of imaging and LFTs. The total cost for all assays was £7380. £6165 was spent on inappropriate requests or where the diagnosis was not pancreatic malignancy. <h3>Conclusion</h3> The clinical utility of CA19.9 is poor with only 7% of samples resulting in a new diagnosis of pancreatic malignancy. The assay is frequently requested inappropriately, often without abdominal imaging being available. LFTS should not be used to guide testing. CA19.9 measurement should only be undertaken in patients where imaging results are available and suggestive of pancreatic malignancy. There are significant cost savings from this approach. <h3>Competing interests</h3> None declared.
Preliminary Observations on Management of Diabetes with "Stabinol"
Authors: M. F. Healy, J. D. Arneaud
Journal: BMJ (1960)

The management of diabetes by oral preparations has now become commonplace in many countries throughout the world.The literature on this subject is voluminous and the drugs in use have been given to more than half a million diabetics.Of all the hypoglycaemic agents tolbutamide has been the most widely used, and to date has the smallest incidence of abnormal side-effects.Mehnert et al. (1958), in a recent review of the use of tolbutamide on a group of 1,030 patients for a period of 1 to 20 months, demonstrated that it produced good control on 52.6% and fair control on an additional 18.5%.Krall and Camerini-Davalos (1958) have reported their results with DBI in a series of 121 patients.They found it to be an effective hypoglycaemic agent in 86%, but therapy had to be discontinued in 18% because of sideeffects affecting mainly the gastro-intestinal tract.The report of Baender (1959) on the comparative toxicology and pharmacology of tolbutamide, chlor- propamide, and metahexamide, showed that compounds with greater toxicity than tolbutamide are of no particular value in the management of diabetes.He pointed out that the price to be paid for lower drug dosage should never be greater toxicity.Davis et al. ( 1959) have reported on the use of R.P. 2259, a sulphathiadiazole (2-sulphamido-p-aminobenzene-5-ter-butyl-1,3,4-thiadiazole; " glipasol ").This report showed R.P. 2259 to be a relatively toxic substance with a very large incidence of liver damage.McColl (1960) presented his findings on the hypoglycaemic activity of a group of substituted thiadiazoles, synthesized by Chubb and Nissenbaum (1959), which, like tolbutamide, have no antibacterial properties.
ADMINISTRATION OF COD LIVER OIL
Authors: H. B. Young
Journal: JAMA (1927)

<h3>To the Editor:</h3> —I am prompted by Dr. Gerstenberger's note on "The Administration of Cod Liver Oil" (The Journal, January 22, p. 243) to offer as a supplement the rules laid down more than fifty years ago by my father, the late Dr. John A. Young of Monmouth, Ill., and which, as he did, I have found 99 per cent effective; namely: The habit should be acquired by taking it "straight"; but an oil of first quality that is not old enough to be rancid should be used. The first dose should be a small one—not more than a half teaspoonful; the mouth should be chilled with ice, or ice-water, and the spoon should be chilled in like manner. Clamping the nostrils will further eliminate the odor. The oil should be taken before, not after, meals.
Radiation Therapy of Some Dermatologic Disorders
Authors: Anthony C. Cipollaro
Journal: New England Journal of Medicine (1954)

THE discovery of x-rays by Roentgen in 1895 opened a new epoch in the field of medicine. These rays were soon used for diagnosis and treatment, and today ionizing radiations hold a preeminent position in dermatologic therapeutics. Perhaps the most important therapeutic agent in the armamentarium of the dermatologist is the x-ray machine. The dermatologist recognizes the inherent dangers pertaining to the use of all forms of ionizing radiations; yet their proper use renders these agents safe.Formerly, x-rays were used for the treatment of many dermatoses for which there are better methods of treatment today. Erysipelas, for example, responds . . .
Early Medication Discontinuation on Long-term Recovery Outcome in First-Episode Psychosis—Reply
Authors: Lex Wunderink, Sjoerd Sytema
Journal: JAMA Psychiatry (2014)

In Reply Undurraga et al comment on 3 methodological issues they perceived in our article.1 First, they state that both interventions were similar because ultimately only a small number of patients discontinued treatment and the mean doses used were arguably significantly different.
Extracorporeal polypectomy of a large rectal polyp
Authors: N. Oruc, O. Ozutemiz, A. Musoglu, T. Ilter
Journal: Endoscopy (2009)

Endoscopic polypectomy of large rectal polyps located close to the anal canal is a technical challenge for endoscopists [1]. It is sometimes impossible to use endoscopic techniques to remove the polyp and the patients are referred for surgical treatment [2].
Rheumatoid factors isolated from patients with autoimmune disorders are derived from germline genes distinct from those encoding the Wa, Po, and Bla cross-reactive idiotypes.
Authors: K D Victor, I Randen, K Thompson, O Forre, J B Natvig, S M Fu, J D Capra
Journal: Journal of Clinical Investigation (1991)

To better understand the structural basis for rheumatoid factor activity, the nucleotide sequence of the light chain variable regions of nine human monospecific IgM rheumatoid factors were analyzed. Rheumatoid factors were isolated from three patients with rheumatoid arthritis, a patient with systemic lupus erythematosus, and a normal individual. The VL gene segments used by these rheumatoid factors are not as restricted as previous work on mixed cryoglobulin rheumatoid factors had suggested. Each of the different VK families is represented and there are two examples where a V lambda gene segment is used. Molecules with structures similar to those of the Wa and Po CRI, characteristic of mixed cryoglobulin rheumatoid factors, are not common among these rheumatoid factors isolated from patients with rheumatoid arthritis. While there are clear examples of rheumatoid factors that are direct copies of germline genes, most of the sequence data suggest that the processes of antigenic selection and somatic mutation contribute significantly to the generation of monospecific rheumatoid factors in patients with autoimmune disease.
218 MIR141 AND MIR200C REGULATE PROGENITOR CELL FEATURES IN HEPATOCELLULAR CARCINOMAS
Authors: O. Govaere, J. Berkers, L. van Kempen, K. Van den Eynde, M. Komuta, B. Spee, R. Aerts, B. Topal, F. Nevens, E. Lerut, J. Van den Oord, T. Roskams
Journal: Journal of Hepatology (2011)
The active site of HIV‐1 protease
Authors: Peter P. Mager
Journal: Medicinal Research Reviews (2001)

Abstract The active site of the homodimeric HIV‐1 protease includes six amino acids (triads AspThrGly found in each monomer) in amino acid positions 25 to 27 and 25′ to 27′. Up to now, the role of Thr26 and Thr26′, and Gly27 and Gly27′, is unknown. It is hypothesized that strong hydrogen‐bonding forces between the Thr26 and Thr26′ residues stabilize the conformational state of the active site, and that the function of Gly27 and Gly27′ is to accommodate and bind a substrate in a position in which the catalytic Asp25 and Asp25′ carboxylate groups can attack the amide moiety of a substrate. © 2001 John Wiley &amp; Sons, Inc. Med Res Rev, 21, No. 4, 348–353, 2001
881 ALTERED EXPRESSION OF DEATH RECEPTORS AND THEIR LIGANDS AS A MECHANISM FOR ENHANCED CD4+ T CELL APOPTOSIS IN HIV/HCV CO-INFECTION
Authors: C. Koerner, F. Tolksdorf, D. Schulte, B. Kraemer, M. Coenen, H.-D. Nischalke, T. Sauerbruch, J. Nattermann, J.K. Rockstroh, U. Spengler
Journal: Journal of Hepatology (2009)
Screening for Down's syndrome based on individual risk.
Authors: M Lewis, M J Faed, P W Howie
Journal: BMJ (1991)

OBJECTIVE--To evaluate the effectiveness of biochemical screening of individual pregnancies for Down9s syndrome risk. DESIGN--Retrospective determination of risk. SETTING--Obstetric and cytogenetic services in Tayside, Scotland. SUBJECTS--3436 pregnant women who had screening for neural tube defects in the second trimester during November 1988 to March 1990 and whose pregnancies were dated by ultrasonography. Three women with pregnancies associated with Down9s syndrome reported later in 1990. MAIN OUTCOME MEASURES--Individual risk calculated from age at estimated date of delivery; chorionic gonadotrophin and alpha fetoprotein concentrations in serum samples obtained at precisely determined gestational ages in second trimester. Results of karyotype determination and outcome of pregnancy. RESULTS--During November 1988 to March 1990 karyotypes were determined for 5% of pregnancies for reasons of maternal age and genetic history and one of the eight affected fetuses was detected. Individual risk could not be calculated for 347 pregnancies, but screening on this basis would have detected five of the cases and required screening in 194 out of 3089 (6.3%) pregnancies; all three affected pregnancies reported later in 1990 would also have been detected, giving a success rate of 73% (95% confidence interval 39% to 94%). The age distribution of women according to individual risk suggests that women over 35 would be screened effectively. CONCLUSION--Screening based on individual risk would use resources more effectively than screening based on maternal age and genetic history without affecting detection rates in older women.
Public Privates: Performing Gynecology from Both Ends of the Speculum
Authors: Leslie Hartley Gise
Journal: JAMA (1997)

How could a book about pelvic examinations be interesting?<i>Public Privates</i>is intersting—and radical, political, and extreme—yet it contains little-known information and enlightening perspectives. It might seem strange that someone would write a book about pelvic examinations, but the author is a gynecology teaching associate (GTA), and 25 years ago, when GTAs began to teach breast and pelvic examinations to medical students, that seemed strange. Now it is commonplace, a valued and accepted way of teaching. (Since the teaching has changed, perhaps the practice of pelvic examination might also change. Criticism of traditional practice emerged with the women's movement of the 1970s, and reformers advocated the idea of women inserting their own speculums and looking at their cervixes. To date, this practice is not widespread but it would seem a useful option for selected patients.) Although paternalistic practices have been reduced over the past 25 years thanks to the
Bone marrow endothelium-targeted therapeutics for metastatic breast cancer
Authors: Junhua Mai, Yi Huang, Chaofeng Mu, Guodong Zhang, Rong Xu, Xiaojing Guo, Xiaojun Xia, David E. Volk, Ganesh L. Lokesh, Varatharasa Thiviyanathan, David G. Gorenstein, Xuewu Liu, Mauro Ferrari, Haifa Shen
Journal: Journal of Controlled Release (2014)
The Origin and Conservation of Epidermal Specificities
Authors: R. E. Billingham, Willys K. Silvers
Journal: New England Journal of Medicine (1963)

Conservation of the Multiplicity of Epidermal Variants throughout LifeThrough practically its entire extent the germinal layer of the epidermis of adult skin displays a high degree of uniformity.3 No structural or other qualitative "markers" have so far been discovered that enable any useful or meaningful distinction to be drawn between basal layer cells of lingual epithelium, sole-of-foot epithelium, corneal epithelium or that of the matrix of a hair follicle; they all look very similar. To what extent is this similarity indicative of a true equivalence in their fundamental biologic properties and potentialities? The very striking functional and structural differences . . .
Specificity Concepts in Japan
Authors: Y. Ago, M. Sugita, H. Teshima, T. Nakagawa
Journal: Psychotherapy and Psychosomatics (1982)

In this study, the authors discuss whether there are any differences in the acquired factors, such as psychosocial factors, related to the age at the onset of psychosomatic disorders, and whether or not there are any characteristics which can be considered unique to Japanese asthmatic patients. Many firstborns were found in those whose onset age was below 10 or in their teens. In those patients who had the onset of asthma in their 20s or 30s many women suffered problems with their mother-in-law after marriage or with their husbands who were interested only in work. We have also discussed that behind these phenomena, problems of parent-child relationship in early childhood were hidden.
Exchangeable and Total Body Potassium in Patients with Chronic Renal Failure
Authors: K. Boddy, P. C. King, R. M. Lindsay, J. Winchester, A. C. Kennedy
Journal: BMJ (1972)

Total body potassium determined by whole-body monitoring and exchangeable body potassium estimated with (43)K were measured simultaneously in 12 patients with stable chronic renal failure. Values for the exchangeable potassium were obtained after equilibration periods of 24, 48, and 64 hours. The exchangeable body potassium, expressed as a percentage of the total body potassium (mean +/- S.E. of mean), gave values of 60.7 +/- 3.3%, 83.6 +/- 2.7%, and 85.9 +/- 2.7% at 24, 48, and 64 hours respectively. It seems that the equilibration between radioactive and native potassium is incomplete after 24 hours; and that exchangeable potassium measured at this time is not an accurate index of the status of total body potassium in such patients. Furthermore, the finding that the value at 64 hours is significantly less than found in healthy subjects suggests that the exchangeable potassium is a smaller fraction of the total body potassium in patients with chronic renal failure.
IF THE CAT SCRATCHES
Authors: Worth B. Daniels
Journal: JAMA (1960)

To the Editor:—  I was interested in the editorial, If the Cat Scratches, inThe Journal, Aug. 13, page 1665. There is, however, one error, historically, in this editorial. It is stated that Foshay first prepared a skin-test antigen for the diagnosis of the disease. This is incorrect. When Dr. Frank MacMurray and I first became interested in this disease we had extensive correspondence with Dr. Foshay and with Dr. Franklin H. Hanger, Presbyterian Hospital, New York. In our paper, read before the Association of American Physicians, May 1, 1951, we covered the information concerning development of the antigen. This paper was published in the Archives of Internal Medicine , December, 1951, page 736. In that paper we stated that Dr. Hanger had a skin lesion on the finger which developed after gardening. There was a cat in the household, but Dr. Hanger had no history of scratch. He developed suppurative
A METHOD FOR IMMEDIATE TREATMENT OF FRACTURED PATELLA
Authors: Frank P. Corrigan
Journal: JAMA (1926)

A part of this method was first demonstrated to me by Professor Bardenheuer of Cologne, Germany, in 1910. It consists of plaster extensions, one applied to the anterior part of the thigh over the quadriceps femoris group of muscles, the other applied over the anterior tibial group. These extensions pass through each other in a way devised, I believe, by Bardenheuer, and called by him "durch greifende zug," or what might be roughly translated as a "through and through pull." The results demonstrated in the Cologne clinic had led me to adopt his method in certain cases. I have used it for a number of years with results that compare favorably with the operative treatment. Especially have I found it useful preliminary to operations and in cases in which operation was contraindicated. During the last eighteen months I have been using another method
Tanning, protection against sunburn and vitamin D formation with a UV-A 'sun-bed'
Authors: M.S. DEVGUN, B.E. JOHNSON, C.R. PATERSON
Journal: British Journal of Dermatology (1982)

Journal Article Tanning, protection against sunburn and vitamin D formation with a UV‐A 'sun‐bed' Get access M.S. DEVGUN, M.S. DEVGUN Department of Biochemical Medicine, Ninewells Hospital, Dundee Search for other works by this author on: Oxford Academic Google Scholar B.E. JOHNSON, B.E. JOHNSON Department of Dermatology, Ninewells Hospital, Dundee Dr B.E.Johnson, Department of Dermatology, Ninewells Hospital, Dundee DD1 9SY. Search for other works by this author on: Oxford Academic Google Scholar C.R. PATERSON C.R. PATERSON Department of Biochemical Medicine, Ninewells Hospital, Dundee Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 107, Issue 3, 1 September 1982, Pages 275–284, https://doi.org/10.1111/j.1365-2133.1982.tb00357.x Published: 01 September 1982 Article history Accepted: 20 November 1981 Published: 01 September 1982
The imagery debate: Déjà-vu all over again?
Authors: Peter P. Slezak
Journal: Behavioral and Brain Sciences (2002)

The imagery debate re-enacts controversies persisting since Descartes. The controversy remains important less for what we can learn about visual imagery than about cognitive science itself. In the tradition of Arnauld, Reid, Bartlett, Austin and Ryle, Pylyshyn's critique exposes notorious mistakes being unwittingly rehearsed not only regarding imagery but also in several independent domains of research in modern cognitive science.