tbuckley/cabot-search huggingface dataset:
The therapeutic importance of understanding mechanisms of neuronal cell death in neurodegenerative disease
Authors: Todd E Golde
Journal: Molecular Neurodegeneration (2009)

Despite major advances in our understanding of the initiating factors that trigger many neurodegenerative disorders, to date, no novel disease-modifying therapies have been shown to provide significant benefit for patients who suffer from these devastating disorders. As most neurodegenerative disorders are late-onset, slowly progressive, and appear to have long relatively asymptomatic prodromal phases, it is possible that therapies optimally targeting the triggers of these disorders may have limited benefit when treatment is initiated in the symptomatic patient. Such therapies may work in the prodromal phase, or when given prophylactically, but in the symptomatic patient there simply may be too much damage to the neuronal networks to restore functionality by reducing or even eliminating the primary stressor. As functional neuronal demise and overt neuronal death are almost certainly the key factors that mediate the functional impairment, it is clear that preventing neuronal death and dysfunction will have a huge clinical benefit. Unfortunately, we lack a detailed understanding of neuronal death pathways in almost all neurodegenerative disorders. To rationally develop new disease modifying therapies that target steps in the degenerative cascade downstream of the disease trigger will require a number of factors. First, we need to refocus our basic research efforts on identifying the precise steps in the pathological cascade that lead to neuronal death in each neurodegenerative disease and, if possible, determine the relative placement of those events within a potentially very complex cascade. Second, we will need to determine which of these steps are potentially targetable. Finally, we will need to develop novel therapies that interfere with these steps and demonstrate that such therapies alone, or in combination with therapies that target the trigger of these devastating diseases, have clinical benefit.
FURTHER CONTRIBUTIONS TO KERATOMETRY.Read in the Section of Ophthalmology, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C., May, 1891.
Authors: SWAN M. BURNETT
Journal: JAMA (1891)

It is now nearly seven years since I began to use the ophthalmometer of Javal and Schiotz daily in my practice, and six years since I published my first results from its use. I appreciated the great practical value of the instrument from the beginning, and have persistently attempted to keep its importance as an instrument of diagnosis in astigmatism before the profession. For a time the apathy and indifference to its value were as intense here as they still seem to be in England and Germany, but recently there have been evidences of a greater interest in the instrument, so that, whereas six years ago, so far as I am aware, there were only three in use in this country, there is now, I understand, difficulty in getting orders for it filled. In my Treatise on Astigmatism, I made the statement that I regarded it as the most important
The behavior-cognition link is well done; the cognition-brain link needs more work
Authors: Walter J. Freeman
Journal: Behavioral and Brain Sciences (2001)

Thelen et al. have a strong case for linking behavior with mind through nonrepresentational dynamics. Their case linking mind with brain is less compelling. Modified avenues are proposed for further exploration: greater emphasis on the dynamics of perception; use of chaotic instead of deterministic dynamics with noise; and use of intentionality instead of motivation, taking advantage of its creative dynamics to model genesis of goal-directed behaviors.
Upper Airway Obstruction in Euthyroid Goiter
Authors: Ramon Jauregui
Journal: JAMA (1977)

Although it is recognized that an enlarged thyroid may occasionally cause tracheal compression, the incidence in euthyroid goiter is unknown. Twenty patients with nontoxic goiter were investigated for upper airway obstruction. Although none of them had dyspnea as a chief complaint, on direct questioning 9/20 had a history of shortness of breath on exertion and choking sensation. Upper airway obstruction was detected in 7/20 (35%) by roentgenography, 12/20 (60%) by flow volume loop (FVL), and in 16/20 (80%) by combined roentgenography and FVL. After therapy for goiter, there was a reduction in the size of the goiter and an improvement in FVL in the whole group. The statistically significant change occurred in peak expiratory flow (P less than .01) and peak inspiratory flow (P less than .05). These findings and the change in configuration of the curve suggested less upper airway compression. We conclude that goiter often causes unsuspected upper airway obstruction, usually slow in onset and not noticed by the patient.
Vaginal Delivery under Caudal Analgesia after Caesarean Section and other Major Uterine Surgery
Authors: F. P. Meehan, A. S. Moolgaoker, J. Stallworthy
Journal: BMJ (1972)

In the absence of a recurring indication for caesarean section vaginal delivery in subsequent pregnancy is a "trial of scar," with potentially serious implications for mother and baby. Labour under caudal analgesia was carefully supervised for 75 women with a surgically scarred uterus-due to lower segment section in 72, abdominal hysterotomy in one, and transcavity myomectomy in two. Every caesarean scar was assessed digitally during labour and every uterus was examined after delivery. Caudal analgesia provided a painless labour and delivery and made scar assessment easy. Controlled intravenous Syntocinon infusion was given to 25 patients. One scar dehiscence occurred early in labour and one in the second stage. Seventy mothers had 71 vaginal deliveries with one pair of twins and one breech. There was one stillbirth and no neonatal death. There were five repeat sections.
Arterial compliance changes in diabetic normotensive patients after angiotensin converting enzyme inhibition therapy
Authors: Athanasios J. Manolis, Stella Iraklianou, Andreas Pittaras, Michael N. Zairis, George Psaltiras, E. Loukatzikou, E. Koutsi, Maria Koutsouridaki, Stefanos Foussas
Journal: Journal of the American College of Cardiology (2003)
NICE should expand its role to cover quality in the NHS, says Darzi
Authors: L. Hitchen
Journal: BMJ (2008)

Quality and evidence of quality should become part of “everyday life” for NHS staff and patients, the health minister Ari Darzi told the 2008 conference of the National Institute for Health and Clinical Excellence (NICE) on 3 December.

Lord Darzi praised the institute for becoming “an established part of the NHS landscape” and for helping to improve the care of millions of NHS patients in its 10 years of existence. But he said that the next step was for NICE to expand its role to encompass quality.

Mike Rawlins, chairman of NICE, said that the organisation’s future work would be influenced by the final report of Lord Darzi’s NHS next stage review, …
Local purchasing of health services is hindering improvements in cancer services
Authors: Susan Mayor
Journal: BMJ (2004)

Lack of experience and expertise in health services at a local level is hindering the purchase of cancer drugs, equipment, and services in the NHS in England, says a parliamentary report published this week.

The report, The Future of Cancer Services in England, found that recent government changes in the way that cancer services are funded and organised—with a shift to purchasing by primary care trusts—were hindering progress in reducing delays in the diagnosis and treatment of cancer and in eliminating variations in cancer treatment in different areas, so called postcode prescribing.

The report, published by …
Adenylate cyclase responsiveness to hormones in various portions of the human nephron.
Authors: D Chabardès, M Gagnan-Brunette, M Imbert-Teboul, O Gontcharevskaia, M Montégut, A Clique, F Morel
Journal: Journal of Clinical Investigation (1980)

The action sites for parathyroid hormone (PTH), salmon calcitonin (SCT), and arginine-vasopressin (AVP) were investigated along the human nephron by measuring adenylate cyclase activity, using a single tubule in vitro microassay. Well-localized segments of tubule were isolated by microdissection from five human kidneys unsuitable for transplantation. PTH (10 IU/ml) increased adenylate cyclase activity in the convoluted and the straight proximal tubule, in the medullary and cortical portions of the thick ascending limb, and in the early portion of the distal convoluted tubule (corresponding stimulated:basal activity ratios were 64, 19, 10, 18, and 22, respectively). SCT (10 ng/ml) increased adenylate cyclase activity in the medullary and cortical portions of the thick ascending limb, in the early portion of the distal convoluted tubule, and, to a lesser extent, in the cortical and the medullay collecting tubule (activity ratios were 7, 14, 15, 3, and 3, respectively). AVP (1 microM) stimulated adenylate cyclase activity in the terminal nephron segments only, i.e., the late portion of the distal convoluted tubule, the cortical and medullary portions of the collecting tubule (activity ratios 81, 51, and 97, respectively). As measured in one experiment, nearly one-half maximal responses were obtained with 0.1 IU/ml PTH or 0.3 ng/ml SCT in thick ascending limbs and with 1 nM AVP in collecting tubules, suggesting that enzyme sensitivity to hormones as well preserved under the conditions used in this study.
PET/CT Staging and Response Evaluation of Post-Transplantation Lymphoproliferative Disease (PTLD)
Authors: Fahmid U. Chowdhury, Fintan Sheerin, Kevin M. Bradley, Fergus V. Gleeson
Journal: Clinical Nuclear Medicine (2009)

A 40-year-old man presented with nonspecific chest pain 14 months following a cadaveric renal transplant for diabetic nephropathy. He was on immunosuppressive therapy with tacrolimus. Computed tomography (CT) of the chest demonstrated a destructive rib lesion with a large soft tissue component. Core biopsy confirmed a diagnosis of monomorphic post-transplantation lymphoproliferative disease strongly positive for Epstein-Barr virus. Staging fluorodeoxyglucose positron emission tomography (PET)/CT detected hypermetabolic osseous lesions, involvement of several nodal groups, and focal uptake within the liver. After reduction of immunosuppression, a follow-up PET/CT scan showed complete metabolic remission. This case highlights the utility of fluorodeoxyglucose PET/CT in the staging and response evaluation of post-transplantation lymphoproliferative disease.
Osteoarthritis of the Knee
Authors: David T. Felson
Journal: New England Journal of Medicine (2006)

A 66-year-old woman who is overweight reports bilateral knee pain of gradual onset during the past several months that increasingly has limited her activities. Last week, when walking down the stairs, she nearly fell when her knee gave way. She does not recall having injured her knee, and she has no morning stiffness and no pain in other joints. She has tried taking up to eight extra-strength (500 mg each) acetaminophen tablets daily without success and has never had ulcers or stomach bleeding. How should the patient be evaluated and treated?
Dietary intake and plasma lipid levels: lessons from a study of the diet of health conscious groups.
Authors: M Thorogood, L Roe, K McPherson, J Mann
Journal: BMJ (1990)

AIM--To re-examine the contentious relation between diet and plasma lipids within a population. DESIGN--Cross sectional sample from a large prospective cohort study of people eating different diets in Britain. Blood samples and diet records collected from subjects. SUBJECTS--Volunteers eating one of four distinct diets--namely, vegans, vegetarians, fish eaters who do not eat meat, and meat eaters. 52 Subjects selected from each group. METHODS--Examination of the relation between nutritional intake recorded in a four day dietary record and plasma lipid concentrations of subjects measured in blood samples collected previously. RESULTS--After controlling for age, sex, and body mass index, the correlation between plasma total cholesterol and the Keys score (which includes dietary cholesterol and saturated and polyunsaturated fat) was 0.37 (p less than 0.001). The mean saturated fat intake in all groups was low (6-14% of energy), but polyunsaturated fat intake was high, so mean total fat intake was generally above that recommended. A high dietary fibre intake was not associated with high carbohydrate intake. Plasma high density lipoprotein values were not associated with any measure of fat intake, but there was a significant correlation of 0.24 between high density lipoprotein values and alcohol intake. CONCLUSIONS--The nature rather than quantity of dietary fat is an important determinant of cholesterol concentrations. Health conscious individuals select a fat modified, rather than a low fat--high carbohydrate diet. National cholesterol lowering dietary advice should be reconsidered.
BILATERAL DUPLICATION OF THE URETERS.
Authors: LOUIS A. LEVISON
Journal: JAMA (1904)

<h3>History.</h3> —G. F., male, aged 65, was admitted to the county hospital Feb. 15, 1904, presenting signs and symptoms of advanced pulmonary tuberculosis. He died Feb. 25, 1904. <h3>Autopsy.</h3> —Both lungs were tubercular. Beside this condition, there were several interesting anatomic anomalies. The transverse colon was U-shaped, nearly reaching the pelvis. The liver presented a number of deep fissures across the phrenic surface, extending in an anteroposterior direction. From the left lobe of the liver an additional long, flaplike lobe, projected toward the left. Each kidney showed pathologic as well as anatomic changes. The left kidney measured 11x5x3 cm. and showed evidences of contraction from a chronic inflammatory change. The right kidney was markedly atrophic. It measured 7x3x2 cm. and presented changes similar to the left kidney. From each kidney arose two fully developed ureters, each having a separate pelvis, but the two ureters on each side entered the bladder through
Factors Associated with Poor Response to Lithium Carbonate: A Clinical Study
Authors: MICHAEL S. ARONOFF, RICHARD S. EPSTEIN
Journal: American Journal of Psychiatry (1970)

Eighteen patients with intermittent manic illness were treated with lithium on a regular basis for an average of two years. An attempt was made to characterize factors related to suboptimal treatment response. A "crisis" state in reaction to a stressful event was observed in suboptimal responders at the time of lithium failure, and a concurrent rise in urinary 17-hydroxycorticosteroid excretion was noted. Possible relationships among lithium ion, metabolic factors, and altered clinical state are discussed.
Youngest England: Some Facts not Sufficiently Recognised relating to the Population under 5 years of Age in England, and especially in London
Authors: D. Biddle
Journal: BMJ (1894)

seen at 4-P.M., when, on examining his mouth, many alveo- lar abscesses were found, due to numerous carious stumps.An effort was made by the dental surgeon to extract the stumps, but the boy, being unable to bear the pain, at his own and his mother's request, it was decided to give an ancesthetic, chloroform being decided upon.Before beginning the administration his chest was care- fully examined, and no cardiac affection or other contra- indication being found he was put under chloroform (Duncan and Flockhart's).The boy took the aneesthetic well, and, the right side of the lower jaw having been cleared of stumps, he began to show signs of coming out.A little more chloroform was given and the left side of the jaw proceeded with.As the fourth stump was being drawn from this side the boy began showing signs of coming round; he suddenly became exceedingly pale, and respiration ELtopped.His head was at once lowered and artificial respiration commenced.After continuing this for about two minutes he took about twenty voluntary respirations, but even during this time neither pulse nor heart impulse could be felt.Artificial respiration was continued, oxygen gas administered, ether and brandy given hypodermically, friction, the battery, and suspension, but, in spite of these efforts being maintained for an hour, he showed no further sign of life.On the following day, August 18th, a coroner's inquest was held and the following verdict returned, "Death whilst under chloroform, which was properly and rightly administered."Mr. P. E. DAVIES read, at the last meeting of the Kidder- minster Medical Society, notes on a fatal case of chloroform ansesthesia which occurred in the Kidderminster Infirmary on September 9th.The patient was a man aged 54, who at one time kept a public-house, and-was well known to be of intemperate habits.He had suffered from an inguinal hzernia for some years.During a " drinking bout" the hernia became strangulated, and when Mr. J. Lionel Stretton was called in he was in great pain, and vomiting faecal matter.On arrival at the infirmary he was in a very depressed condition; and seemed to have an unusual dread of the opera- tion, remarking several times to the nurse that " he would not get through it."The heart was auscultated, and nothing abnormal dis- covered.Ether was first administered with Clover's inhaler, the usual amount (A ij) being used.Owing to the violent and persistent struggling it was found impossible to get him
Is Residency Training Really Harmful?-Reply
Authors: Charles Rainey
Journal: JAMA (1997)

<h3>To the Editor.</h3> —The intention of my article was to call attention to the human costs of today's medical training system both for the patient and the physician and to suggest ways to improve that system as health care reform evolves. It was based on Duncan's book, in which he researched and documented postgraduate medical education in the United States in the 1990s. Duncan surveyed a variety of hospitals and specialties, and he cited specific references to support his observations. I believe he met the scientific muster that our profession demands in research. He relays his conversations with many leaders in medical education, including Bertrand Bell, MD, and John Stobo, MD. Both of these distinguished physicians and Duncan agreed that the current system is costly to patients, residents, and payors and is in need of change. I feel as though I am in good company. The 3 main points remain. First, long hours
Topical treatments for chronic plaque psoriasis of the scalp: a systematic review
Authors: A.R. Mason, J.M. Mason, M.J. Cork, H. Hancock, G. Dooley
Journal: British Journal of Dermatology (2013)

Chronic plaque psoriasis is the most common type of psoriasis and is characterized by redness, thickness and scaling. First-line management is with topical treatments.Our objective was to establish the effectiveness, tolerability and safety of topical treatments for people with chronic plaque psoriasis of the scalp, assessing placebo-controlled trials of all treatments and head-to-head trials that assessed vitamin D analogues.As part of a Cochrane review of topical treatments for psoriasis, we systematically searched electronic databases for randomized controlled trials. The review included 26 randomized controlled trials of treatments for psoriasis of the scalp with 8020 participants. Trials used several measures to assess changes in psoriasis severity: these were combined using the standardized mean difference metric and interpreted by reporting as a six-point global improvement score.On effectiveness grounds, very potent or potent steroid treatments should be preferred to vitamin D3 analogue with approximately an average 10% additional improvement on a six-point scale. Vitamin D3 analogue combined with potent steroid appears slightly more effective than potent steroid monotherapy (3% additional improvement on a six-point scale). Rates of withdrawal from treatment and adverse events in trials were generally low and similar to those for placebo. There remains uncertainty about the atrophic potential of corticosteroid treatments for scalp psoriasis.Corticosteroids are more effective than vitamin D analogues and similarly tolerated. However, further research is needed to inform long-term maintenance treatment and provide appropriate safety data.
Does random blood glucose sampling outdate testing for glycosuria in the detection of diabetes during pregnancy?
Authors: T Lind, J Anderson
Journal: BMJ (1984)

A random blood glucose concentration was determined in 2403 pregnant women attending an antenatal clinic at between 28 and 32 weeks9 gestation. The calculated 99% cut off values were 6.1 mmol/l (110 mg/100 ml) within two hours after a meal and 5.6 mmol/l (101 mg/100 ml) more than two hours after a meal. Patients with a blood glucose concentration in excess of these values were referred for a 75 g oral glucose tolerance test. Of 59 referred, four were found to have previously unsuspected but unequivocal diabetes mellitus and another four to have impaired glucose tolerance on the basis of the World Health Organisation9s criteria. Screening all antenatal patients by randomly measuring blood glucose concentrations is not only cheap and efficient but also does not interfere with the routine of busy antenatal clinics.
Interleukin-6 as a Therapeutic Target
Authors: Jean-François Rossi, Zhao-Yang Lu, Michel Jourdan, Bernard Klein
Journal: Clinical Cancer Research (2015)

Abstract Human IL6 is a cytokine produced by many cell types that has pleiotropic effects. In agreement, anti-IL6 therapy reduces inflammation, hepatic acute phase proteins, and anemia and has antiangiogenic effects. Blocking IL6 has demonstrated therapeutic efficacy with drug registration in Castleman disease and inflammatory diseases (rheumatoid arthritis) without major toxicity. Interestingly, the inhibition of C-reactive protein (CRP) production is a trustworthy surrogate marker of anti-IL6 therapy efficacy. Clinically registered IL6 inhibitors include siltuximab, an anti-IL6 mAb, and tocilizumab, an anti-IL6R mAb. In various cancers, in particular plasma cell cancers, large randomized trials showed no efficacy of IL6 inhibitors, despite a full inhibition of CRP production in treated patients in vivo, the numerous data showing an involvement of IL6 in these diseases, and initial short-term treatments demonstrating a dramatic inhibition of cancer cell proliferation in vivo. A likely explanation is the plasticity of cancer cells, with the presence of various subclones, making the outgrowth of cancer subclones possible using growth factors other than IL6. In addition, current therapeutic strategies used in these cancers already target IL6 activity. Thus, anti-IL6 therapeutics are able to neutralize IL6 production in vivo and are safe and useful in inflammatory diseases and Castleman disease. Clin Cancer Res; 21(6); 1248–57. ©2015 AACR.
Y-Fluorescence of Interphase Nuclei, Especially Circulating Lymphocytes
Authors: P. E. Polani, D. E. Mutton
Journal: BMJ (1971)

Application of a fluorescence technique for the detection of the human Y chromosome in interphase nuclei indicates that the best results may be obtained from the study of lymphocytes in blood smears. The most satisfactory Y-fluorescence is obtained with the use of buffered quinacrine mustard dihydrochloride. The method can be complemented by other standard techniques to obtain a clear idea of the sex-chromosome complement of the individual. The application of this technique to clinical and chromosomal diagnosis and to the prenatal detection of the Y chromosome in amniotic cells seems at least as promising as has proved the earlier identification of the Barr body.
Effect of Systemic Inflammation on Inspiratory and Limb Muscle Strength and Bulk in Cystic Fibrosis
Authors: Valérie Dufresne, Christiane Knoop, Alain Van Muylem, Anne Malfroot, Michel Lamotte, Christian Opdekamp, Gaël Deboeck, Marie Cassart, Bernard Stallenberg, Georges Casimir, Jean Duchateau, Marc Estenne
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

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