tbuckley/cabot-search huggingface dataset:
Genetics in Ophthalmology. Vol II: Neuro Ophthalmological Part
Authors: Harold F. Falls
Journal: JAMA (1964)

Ophthalmologists have long been impressed by the significant role of the gene in ocular disease, for the eye is so precise that even minor alterations result in signs and symptoms, and furthermore, superb instruments make it possible meticulously to examine even the innermost structures. Over the past century a most impressive literature has accumulated on hereditary disorders of the eye. Among the more important modern contributors to this literature are the authors of the present work. Beautifully printed, profusely and carefully illustrated, the two volumes are a careful expansion of Dr. Waardenburg's<i>Das menschliche Auge und seine Erbanlagen</i>, for many years the only authoritative book devoted to ophthalmic genetics. The first volume, made available in 1961, and written principally by Waardenburg, begins with a historical review of genetics as related to ophthalmology and then concisely presents the cytological background and principles of genetics. Elementary genetic statistics are reviewed, and the
Diagnosis of pancreatic cancer by contrast-harmonic endoscopic ultrasound (EUS): complementary and not competitive with EUS-guided fine-needle aspiration
Authors: Pietro Fusaroli, Mohamad Eloubeidi
Journal: Endoscopy (2014)

Contrast-harmonic endoscopic ultrasound (CH-EUS) is a relatively new technique, based on observation of a specific tissue harmonic after intravenous injection of an ultrasound contrast agent [1]. SonoVue (sulfur hexafluoride microbubbles; Bracco Imaging, Milan, Italy), the most widely adopted contrast agent, acts as a pure intravascular enhancer; intraprocedural observation of the microvasculature of the lesion of interest is achieved and compared with that of the surrounding parenchyma and vessels. Researchers have identified different patterns of SonoVue uptake in pancreatic tumors, and classified them into three broad categories: hypoenhanced, isoenhanced, and hyperenhanced. Further classification can be derived by analyzing the network of vessels (homogeneous or inhomogeneous) and the timing of contrast washout (fast washout during the arterial phase or slow washout during the venous phase).
Master's degree in general practice
Authors: D Cox
Journal: BMJ (1994)

appreciable number of senior house officers enter general practice and therefore there will be many departments with a two day shortfall in senior house officers.The NHS executive must be reminded that senior house officers do not rotate endlessly within the NHS hospitals, but follow a career path.Any plans for changing the start dates of house officers must take into account the end points of these career paths, which may lie outside NHS hospitals.
Expression of hypoxia-inducible transcription factors in developing human and rat kidneys
Authors: W.M. Bernhardt, R. Schmitt, C. Rosenberger, P.M. Münchenhagen, H.-J. Gröne, U. Frei, C. Warnecke, S. Bachmann, M.S. Wiesener, C. Willam, K.-U. Eckardt
Journal: Kidney International (2005)
Diabetes Insipidus after Tuberculous Meningitis
Authors: D. R. Hay
Journal: BMJ (1960)

comment on the card of one child aged 7: " Fracture reduced under pethilorfan.Considerable force used during reduction with absolutely no pain; the child did not even wince."The failures comprised one dislocation of the elbow, one fractured femur in a young and muscular man, and one case of "locked knee" ; two of these were later reduced satisfactorily under a general anaesthetic.No side-effects or complications were observed in any of the cases described above.This technique has revolutionized our work in the casualty department.The need for an anaesthetist is much less frequent, fractures and dislocations can be reduced immediately even if the patient has recently had a meal, and patients can usually go home immediately the post-reduction x-ray film has been taken.
The Threshold Approach to Clinical Decision Making
Authors: Stephen G. Pauker, Jerome P. Kassirer
Journal: New England Journal of Medicine (1980)

The physician's estimate of the probability that a patient has a particular disease is a principal factor in the determination of whether to withhold treatment, obtain more data by testing, or treat without subjecting the patient to the risks of further diagnostic tests. Using the concepts of decision analysis, we have derived expressions for two threshold probabilities involved in this choice: a "testing" threshold and a "test-treatment" threshold. Values can be assigned to these thresholds from data on the reliability and potential risks of the diagnostic test and the benefits and risks of a specific treatment. Treatment should be withheld if the probability of disease is smaller than the testing threshold, and treatment should be given without further testing if the probability of disease is greater than the test-treatment threshold. The test should be performed (with treatment depending on the test outcome) only if the probability of disease is between the two thresholds. The method exposes important principles of decision making and helps the clinician develop a rational, quantitative approach to the use of diagnostic tests.
WAON THERAPY UP-REGULATES THE HSP90 AND LEADS TO ANGIOGENESIS THROUGH AKT-ENOS PATHWAY IN A MOUSE MODEL OF HINDLIMB ISCHEMIA
Authors: Takahiro Miyauchi, Masaaki Miyata, Yoshiyuki Ikeda, Yuichi Akasaki, Narisato Hamada, Takahiro Shirasawa, Hideyuki Eto, Furusho Yuko, Shuichi Hamasaki, Chuwa Tei
Journal: Journal of the American College of Cardiology (2010)
Probability of Middle-Aged Men Developing Coronary Heart Disease in Five Years
Authors: ANCEL KEYS, CHRIST ARAVANIS, HENRY BLACKBURN, F. S. P. VAN BUCHEM, RATKO BUZINA, B. S. DJORDJEVIC, FLAMINIO FIDANZA, MARTTI J. KARVONEN, ALESSANDRO MENOTTI, VITTORIO PUDDU, HENRY L. TAYLOR
Journal: Circulation (1972)

Characteristics of 11,132 men aged 40-59 years and free from coronary heart disease (CHD) at entry were related to follow-up experience, using multivariate analysis. In 5 years among 2,404 U. S. railroad men and 8,728 European men there were 615 cases of CHD, 214 of whom died from CHD or suffered definite nonfatal infarction. With five entry characteristics (age, systolic blood pressure, serum cholesterol, smoking habit, and body mass index), multiple logistic solutions for Europeans and Americans, separately, gave estimates of the individual probability of CHD. Classified by deciled scores for these probabilities, the expected and observed CHD cases were highly correlated (r = 0.930-0.981). Predictions based on European data applied to Americans, and vice versa, gave similar high correlations but American incidence was excessive compared with European experience. Application of the analysis coefficients obtained from data in Europe and in the U. S. railroad to 6,221 other U. S. men 40-59 years of age, CHD-free at entry, gave good prediction of relative risk (r = 0.94) for observed versus predicted cases in deciles of risk score; however, the actual numbers of cases were underpredicted. From single measurements of a few characteristics the multiple logistic solution usefully estimates the relative risk of CHD for individuals. Age, systolic pressure, and serum cholesterol are universally powerful predictors of risk. Variables not measured in this study or not yet identified contribute to the risk of CHD among American men.
Alemtuzumab in Previously Treated Chronic Lymphocytic Leukemia Patients Who Also Had Received Fludarabine
Authors: K. R. Rai, C. E. Freter, R. J. Mercier, M. R. Cooper, B. S. Mitchell, E. A. Stadtmauer, P. Santábarbara, B. Wacker, L. Brettman
Journal: Journal of Clinical Oncology (2002)

PURPOSE: This phase II pilot study determined the efficacy and safety of alemtuzumab (Campath-1H; Burroughs Wellcome, United Kingdom) in patients with chronic lymphocytic leukemia (CLL), all of whom had previously received fludarabine and other chemotherapy regimens. PATIENTS AND METHODS: Twenty-four patients were treated with intravenous alemtuzumab at six centers in the United States. The target dose of 30 mg over 2 hours, three times weekly, was administered for up to 16 weeks. Responses were evaluated by an independent panel of experts using 1996 National Cancer Institute–sponsored Working Group criteria. Safety assessments included analysis of lymphocyte subpopulations. Antimicrobial prophylaxis was not mandatory. RESULTS: Eight patients (33%) achieved a major response (all partial remissions), with a median time to response of 3.9 months (range, 1.6 to 5.3 months). The median duration of response was 15.4 months (range, 4.6 to ≥ 38.0 months), the median time to disease progression was 19.6 months (range, 7.7 to ≥ 42.0 months), and the median survival time was 35.8 months (range, 8.8 to ≥ 47.1 months). Acute infusion-related events, mainly grades 1 and 2, were most common and most severe in the first week. Ten patients (eight nonresponders and two responders) experienced major infections on-study. Pneumocystis carinii pneumonia was reported in two patients on-study; neither had received prophylaxis. Median CD4 + and CD8 + counts decreased and then began to increase by the end of the study, with further recovery by 1-month follow-up. One of 53 samples obtained from 10 patients had a low titer of alemtuzumab antibodies. CONCLUSION: Alemtuzumab has significant activity in poor-prognosis, fludarabine-treated CLL patients. However, because of a relatively high incidence of opportunistic infections accompanying profound lymphopenia, future protocols should include mandatory prophylaxis.
PROCUREMENT OF MEDICAL PERSONNEL AND MATÉRIEL IN THE PRESENT EMERGENCY
Authors: JAMES C. MAGEE
Journal: JAMA (1941)

I appreciate the opportunity afforded me this afternoon to express my sincere thanks for the splendid cooperation and support rendered by the Committee on Medical Preparedness of the American Medical Association in the furtherance of the national defense program and to inform you of some of our problems and the action we are taking to solve them in a proper and judicious manner. As physicians and citizens, you have given proof of your interest in national defense. The security of our country is the paramount issue in all our lives today, and everything else must be subordinated to the accomplishment of this purpose. There must be no moral or physical hesitancy until the adequacy of our preparedness insures the national safety of our people. <h3>MEDICAL PERSONNEL PROBLEM</h3> Our problem is not only of securing personnel in order to furnish an adequate medical service to an unprecedented peacetime army but of
The sulphoxidation of S-carboxymethyl-L-cysteine in COPD
Authors: G. B. Steventon, S. C. Mitchell
Journal: European Respiratory Journal (2006)

To the Editors: 

Mucolytics, such as S -carboxymethyl-L-cysteine, have a role to play as an adjunct in the treatment of chronic obstructive airway disease, but their apparent unreliability has led to divided opinion concerning their usefulness 1–3. The failure to achieve any measurable benefit with some patients presumably reflects underlying interindividual differences within the patient cohort, and not that the drug itself is without efficacy. In this respect, one major topic affecting clinical efficacy of a drug is its disposition and fate following administration, and, in particular, those factors that influence its subsequent metabolism and deactivation.

The …
Randomised controlled trial of disclosure of emotionally important events in somatisation in primary
Authors: A. F Schilte, P. J M Portegijs, A. H Blankenstein, H. E van der Horst, M. B F Latour, J. T. M van Eijk, J A. Knottnerus
Journal: BMJ (2001)

To test whether a disclosure intervention improves subjective health and reduces medical consumption and sick leave in somatising patients in general practice.Non-blind randomised controlled trial.10 general practices in the Netherlands.161 patients who frequently attended general practice with somatising symptoms.Patients in the intervention group were visited two to three times and invited to disclose emotionally important events in their life. Control patients received normal care from their general practitioners.Use of medical services (drugs and healthcare visits), subjective health, and sick leave assessed by self completion questionnaires after 6, 12, and 24 months.Of the 161 patients, 137 completed the trial (85%). Both groups were comparable at baseline. The intervention had no effect on the main outcome measures at any point. Intervention patients made one more visit to health care (95% confidence interval -4 to 6); the use of medicines did not change in both groups (-1 to 1); subjective health improved 3.6 points more in the control group (-11.2 to 4.3); and disclosure patients were on sick leave one more week (-1 to 3). Patients often had a depression or anxiety disorder for which they were not receiving adequate care.Although the intervention was well received by patients and doctors, disclosure had no effect on the health of somatising patients in general practice.
Foundation trusts still struggle to hit cancer treatment targets, finds Monitor
Authors: I. Torjesen
Journal: BMJ (2011)

NHS foundation trusts in England have improved their financial performance in the past year, but many are still struggling to meet waiting time targets for cancer services, a report by Monitor, the regulator of foundation trusts, has found.

At the beginning of 2010-11 Monitor identified a number of key challenges that could present major risks to the financial viability of foundation trusts ( BMJ 2010;341:c4438, doi:10.1136/bmj.c4438). Its annual review of trusts’ performance has found that although the financial risks had been largely mitigated, and Monitor took less formal regulatory action in 2010-11 than in the previous year, many trusts were continuing to miss waiting time targets …
Cyclosporine for Plaque-Type Psoriasis
Authors: Charles N. Ellis, Mark S. Fradin, Joseph M. Messana, Marc D. Brown, Michael T. Siegel, A. Howland Hartley, Leslie L. Rocher, Suzanne Wheeler, Ted A. Hamilton, Thomas G. Parish, Mary Ellis-Madu, Elizabeth Duell, Thomas M. Annesley, Kevin D. Cooper, John J. Voorhees
Journal: New England Journal of Medicine (1991)

Severe plaque-type psoriasis has been successfully treated with orally administered cyclosporine, but there has been no comparative, controlled evaluation of various dosages and their efficacy and side effects.
Identification and characterization of a monocyte-derived neutrophil-activating factor in corticosteroid-resistant bronchial asthma.
Authors: J R Wilkinson, A E Crea, T J Clark, T H Lee
Journal: Journal of Clinical Investigation (1989)

Peripheral blood mononuclear cells (PBMC) were isolated from seven normal subjects, eight asthmatic subjects clinically sensitive to corticosteroids (CS), and eight asthmatic subjects clinically resistant to corticosteroids (CR). PBMC were cultured at 37 degrees C for 24 h in the absence or presence of 10(-16) to 10(-4) M hydrocortisone. Calcium ionophore (A23187)-activated neutrophils (PMN) primed by supernatants of PBMC from asthmatic subjects cultured in the absence of hydrocortisone generated approximately threefold more leukotriene B4 than PMN primed by supernatants of PBMC from normal subjects (P less than 0.05). Incubation of PBMC derived from CS subjects with 10(-8) M hydrocortisone completely inhibited the production of the enhancing activity (P less than 0.01), whereas in CR subjects hydrocortisone at concentrations up to 10(-4) M did not suppress the release of enhancing activity. The enhancing activity was produced by monocytes. Enhancing activity eluted with an Mr of 3,000 D and a pI of 7.1. It eluted at 10% acetonitrile after reverse-phase HPLC. The activity was destroyed by heating to 60 degrees C for 60 min and was sensitive to pronase treatment. The purified factor also enhanced superoxide generation by PMN which had been stimulated submaximally by phorbol myristate acetate.
Proarrhythmia as a pharmacogenomic entity: A critical review and formulation of a unifying hypothesis
Authors: D RODEN
Journal: Cardiovascular Research (2005)

Proarrhythmia represents an extreme example of the phenomenon that drug effects vary widely among individuals. Studies of mechanisms leading to proarrhythmia have had important implications for understanding arrhythmogenesis, rational use of antiarrhythmic therapies, selection of patients for specific therapies, and drug development. In addition, because proarrhythmia often seems to develop in the absence of clear risk predictors, a role for genetics in predisposing to this adverse drug reaction has been postulated. This review presents mechanisms whereby genetic factors may contribute to variable drug responses and describes our current understanding of how these mechanisms play a role in proarrhythmia. A unifying hypothesis is presented: physiologic processes (such as drug elimination or cardiac repolarization) include multiple redundancies, and congenital or acquired absence of such redundancies--due to disease, interacting drugs, or genetic makeup--may confer no baseline phenotype, but nevertheless enhance susceptibility to unusual drug responses.
A mask to modify inspired air temperature and humidity and its effect on exercise induced asthma.
Authors: M Nisar, D P Spence, D West, J Haycock, Y Jones, M J Walshaw, J E Earis, P M Calverley, M G Pearson
Journal: Thorax (1992)

Heat and moisture loss from the respiratory tract during exercise are important triggers of exercise induced asthma.A new heat and moisture exchange mask has been developed which both recovers exhaled heat and water and has a sufficiently low resistance for use during exercise. The effect of the mask on inspired air temperature was studied in four normal subjects. Eight asthmatic subjects performed identical exercise protocols on three separate days, breathing room air through a conventional mouthpiece, a dummy mask, and the new heat and moisture exchange mask. Seven different asthmatic subjects exercised while breathing cold air at -13 degrees C through a dummy or active mask.All subjects found the new mask comfortable to wear. The mean inspired temperature when the mask was used rose to 32.5 (1.4) degrees C when normal subjects breathed room air at 24 degrees C and to 19.1 (2.7) degrees C when they inhaled subfreezing air at -13 degrees C. The heat and moisture exchange mask significantly reduced the median fall in forced expiratory volume in one second (FEV1) after exercise to 13% (range 0-49%) when asthmatic subjects breathed room air compared with 33% (10-65%) with the dummy mask and 28% (21-70%) with the mouthpiece. The fall in FEV1 when the asthmatic subjects breathed cold air was 10% (0-26%) with the heat and moisture exchange mask compared with 22% (13-51%) with the dummy mask.Use of a heat and moisture exchange mask can raise the inspired temperature and humidity and ameliorate the severity of exercise induced asthma. The mask may be of practical value in non-contact sport or for people working in subzero temperatures.
Application of Cold to Burns
Authors: J. M. BODENHEIMER
Journal: JAMA (1961)

<h3>To the Editor:—</h3> Under the title "Pain Relief in Burns," inThe Journal, Dec. 10, 1960, page 1194, Dr. Charles Harris, commenting on the treatment of burns by immersion in ice water, records his favorable impression of this treatment which, as he said, he discovered by accident. I wish to add my experience with the use of denatured ethyl alcohol in the immediate treatment of burns which I, too, discovered by accident. One of my friends who owns a restaurant brought his cook to my home after midnight. The cook was suffering from pain as the result of a flash burn of the entire right arm. My armamentarium consisted of a roll of cotton, a 2-in. bandage, and a bottle of denatured ethyl alcohol. After applying cotton soaked in alcohol I bandaged the arm. I was preparing a hypodermic injection of morphine, when the patient exclaimed: "My arm feels fine.
Therapeutic opportunities in vasoocclusive disease.
Authors: J M Ritter, C T Dollery
Journal: Circulation (1986)

There is evidence that aspirin is partially effective in the prophylaxis of various vasoocclusive disorders. This article reviews pharmacologic opportunities for improvement over and above the therapeutic effect of aspirin. It is concluded that several rational possibilities merit consideration, in particular, the use of combinations of drugs that affect the thrombotic process at different points. Such strategies will ultimately require validation by clinical trial.
Book Review Physical Illness and Depression in Older Adults: A Handbook of Theory, Research, and Practice (The Plenum Series in Social/Clinical Psychology.) Edited by Gail M. Williamson, David R. Shaffer, and Patricia A. Parmelee. 370 pp. New York, Kluwer Academic, 2000. $75. 0-306-46269-9
Authors: Samuel Barondes
Journal: New England Journal of Medicine (2001)
Role of Poly-ADP Ribosyltransferase Activation in the Vascular Contractile and Energetic Failure Elicited by Exogenous and Endogenous Nitric Oxide and Peroxynitrite
Authors: Csaba Szabó, Basilia Zingarelli, Andrew L. Salzman
Journal: Circulation Research (1996)

Stimulation of vascular smooth muscle with bacterial lipopolysaccharide (LPS) and proinflammatory cytokines induces the expression of a distinct isoform of NO synthase (inducible NOS [iNOS]) contributing to the suppression of vascular contractility. We have obtained evidence of the involvement of an indirect pathway triggered by NO and its reaction product peroxynitrite (ONOO-) through the activation of the nuclear enzyme poly-ADP ribosyltransferase (PARS) in the pathogenesis of cellular energetic and contractile failure in vascular smooth muscle. Exposure of vascular smooth muscle cells caused DNA strand breaks, activation of PARS, depletion of NAD+, and inhibition of mitochondrial respiration. The NAD+ depletion and inhibition of mitochondrial respiration were reduced by pharmacological inhibition of PARS. Stimulation of vascular smooth muscle cells with LPS and interferon gamma (IFN-gamma) triggered the production of superoxide anion over 3 to 48 hours and NO and ONOO- over 24 to 48 hours and resulted in significant DNA strand breakage. The decrease in mitochondrial respiration in response to LPS and IFN-gamma stimulation was inhibited by the ONOO- scavenger uric acid (100 mumol/L) and by inhibitors of iNOS. The PARS inhibitors 3-aminobenzamide (1 mmol/L), nicotinamide (1 mmol/L), and PD 128763 (100 mumol/L) inhibited the reduction in cellular NAD+ and ATP and the suppression of mitochondrial respiration in response to LPS and IFN-gamma stimulation. Administration of 3-aminobenzamide also reduced PARS activation and vascular hyporeactivity of rat thoracic aortas exposed to ONOO- (300 mumol/L to 1.5 mmol/L) in vitro. 3-Aminobenzamide (10 mg/kg IP) preserved the ex vivo contractility of aortas obtained from endotoxic rats and improved survival in lethal murine endotoxic shock. These data suggest that PARS activation due to iNOS induction (1) is involved in the energetic depletion of vascular smooth muscle cells that express iNOS and (2) contributes to the pathogenesis of vascular energetic and contractile failure in endotoxic shock. Inhibition of PARS may be a novel concept of therapeutic potential in shock.