tbuckley/cabot-search huggingface dataset:
Pancreatitis in sarcoidosis.
Authors: P A McCormick, D Malone, M X FitzGerald, O FitzGerald
Journal: BMJ (1985)

2 observations rares: episodes de pancreatite aigue lies a la sarcoidose. Resultats favorables rapides du traitement par steroides, generalement contre-indique dans la forme courante de pancreatite
Adaptation to Exercise in Angina Pectoris
Authors: REX N. MACALPIN, ALBERT A. KATTUS
Journal: Circulation (1966)

Twelve patients with angina pectoris manifested an ability to adapt to exercise during treadmill stress testing with electrocardiographic monitoring. Three patterns of adaptation were seen. Nine subjects had the ability to continue walking after the onset of angina with eventual disappearance or lessening of anginal pain and the associated ischemic ST-segment depression; anginal pain and ST depression began to diminish during a steady state of blood pressure and heart rate in those cases in which these factors were measured. Four subjects were able to continue walking for long periods of time during a state of angina and ischemic ST depression. Three subjects demonstrated an increase in exercise capacity after being warmed up by a preceding bout of exercise-induced angina; blood pressures and heart rates during the initial, "warming-up" effort tended to be higher than those during the early stages of the second effort. In three subjects more than one of these patterns of adaptation were demonstrated. Five of the subjects showed striking subjective and objective improvement in exercise tolerance while on a program of regular walking exercise. Selective coronary cineangiography was performed in eight of these patients and two patterns of coronary disease were seen: (1) occlusion of a major coronary vessel with good collateral channels circumventing the obstruction; (2) strategically placed, proximal, stenotic lesions in major coronary vessels without frank occlusion and without discernible collateral development. Some diagnostic and therapeutic implications of these findings are discussed.
Single film retrograde umbilical aortography in the diagnosis of hypoplastic left heart syndrome with aortic atresia.
Authors: R Rosengart, J M Jarmakani, G C Emmanouilides
Journal: Circulation (1976)

Single film retrograde umbilical aortography was used successfully in confirming the diagnosis of hypoplastic left heart in three neonates. The method involves injecting Renografin 75% (1.25 cc/kg body weight) into the umbilical artery catheter according to the following sequence. First, the tip of the catheter is positioned at the level of the ductus arteriosus. The infant heart beats are then counted from one to three. The contrast media injection is begun manually on the count of one and an anterior-posterior chest film is taken on the count of three. Thus the film is taken one diastolic period after completion of the injection. The proper timing of the contrast media injection and filming is essential for obtaining a diagnostic film. This procedure was diagnostic in the three infants studied and eliminated the need of transferring two sick infants from affiliated hospitals.
Alosetron: a case study in regulatory capture, or a victory for patients' rights?
Authors: R. Moynihan
Journal: BMJ (2002)

Editorial p 555 News p 561

Senior members of the FDA's advisory committee warn of more deaths if alosetron (Lotronex) is relaunched, as a former insider speaks out about the US regulator's close relationship with Big Pharma 

In April this year, a special joint advisory committee to the United States Food and Drug Administration (FDA) recommended remarketing GlaxoSmithKline's controversial drug for irritable bowel syndrome, alosetron (Lotronex), which was once considered a potential top seller but was voluntarily withdrawn in late 2000 following serious adverse events, including deaths. Because of the drug's modest benefits and major harms, a key condition of the committee's recommendation was the introduction of a “risk management programme.” Committee members emphasised during their deliberations that the drug should be prescribed only by doctors who had been trained and certified to use it. They explicitly rejected a weaker company proposal to allow prescribing by doctors who “self attested” to competency.

#### Box 1: The Lotronex timeline RETURN TO TEXT

Just six weeks later, on 7 June, the FDA formally re-approved marketing, but it announced that prescribing would be based on …
Severe metabolic alkalosis
Authors: T Constans, J L Guilmot, P Chevallier, D Perrotin
Journal: BMJ (1982)

Twenty patients out of 38 (52 60' ) who had undergone haemodialysis for one to 80 months (mean 28 1 months) were found to have eosinophilia (eosinophils > 400/mm3) in a random examination (December 1980) in the first unit, while 16 out of 31 patients (51 6%) whose dialysis had lasted from three to 68 months (mean 29-7 months) had eosinophilia in the second unit.Thirty patients from the latter unit who had received dialysis for 20-72 months, who had eosinophil counts at least once a month, were included in this study also.Sixteen out of 30 of these (5333%) never developed eosinophilia during the observation period, six (20%) developed constant eosino- philia, and eight (26 7%) developed transient eosinophilia.This study also shows that during the first two years there is a progressive increase in the mean eosinophil count of the patients, which remains almost constant during the following years (figure).No correlation was found with 4.00 300-Mean eosinophil count/mm¾3 SE 200 - n= 18 100 Before 1 2 3 4 dialysis Years on dialysisEosinophil counts in patients undergoing dialysis.
Budd-chiari syndrome management: Timing of treatment is an open issue
Authors: Andrea Mancuso
Journal: Hepatology (2013)

I read with interest the long-term multicenter experience on Budd-Chiari syndrome (BCS) step-wise management published in Hepatology.1 As stated before, medical therapy is suggested as the first-line treatment, angioplasty/stenting the second-line, transjugular intrahepatic portosystemic shunt (TIPS) the further step, and liver transplantation (LT) the last chance.2 Step-wise management suggests moving forward when no response to therapy appears. However, definition for response to therapy was not stated,2, 3 and a proposal of such a definition needs validation.4 Interestingly, 20 of the 69 who received only medical therapy died, a high rate considering the availability of further invasive treatments. The remaining 88 underwent invasive treatment, mostly TIPS, 20 LT, and only 3 surgical shunt. Overall survival was 74% at 5 years.1 TIPS is the most used treatment for BCS2, 3 because it is effective also in the case of thrombosis extension to the portal vein tree.5-7 However, timing for TIPS was not stated. Shunt surgery was used in a strict minority of patients in this study.1 Others report surgery as the main indication for BCS, albeit with not uniform survival rates.8 However, given TIPS efficacy,5-7 surgical shunts should be limited to cases not suitable for TIPS.9 Because of the rarity of BCS, management guidelines come from expert opinion, are empirical, and are not evidence based. Given that benefit of treatments for BCS is not under debate, I wonder if anticipating invasive treatments, before no response to medical therapy appears, could decrease hepatic fibrosis development, disease progression, and finally improve outcome. Andrea Mancuso, M.D.1,2 1Epatologia e Gastroenterologia, Ospedale Niguarda Ca' Granda, Milano, Italy 2Medicina Interna 1, Ospedale Civico Palermo, Italy
Response to Vestbo and Rodrigues-Roisin
Authors: Ian D Pavord, Andy Bush
Journal: Thorax (2013)

There was once an Editor of a paper in the far west who was sitting at his desk, musing pleasantly on life, when a bullet crashed through the window and embedded itself in the wall at the back of his head. A happy smile lit up the Editor's face. ‘Ah’, he said complacently, ‘I knew that Personal column of ours was going to be a success!’ What the bullet was to the Far West editor, the letter of Drs Vestbo …
Cell Migration: Tapered Microtract Array Platform for Antimigratory Drug Screening of Human Glioblastoma Multiforme (Adv. Healthcare Mater. 3/2015)
Authors: Junghwa Cha, Ilkyoo Koh, Yemuk Choi, Jungwhoi Lee, Chulhee Choi, Pilnam Kim
Journal: Advanced Healthcare Materials (2015)

Histopathologically, brain tumor cells, especially glioblastoma multiform (GBM) cells, migrate along the orientation of thin, elongated anatomical structures, such as white-matter tracts. On page 405, P. Kim and team show how the thinnest width of tapered microtract array platform can induce the in vivo saltatory migration of brain tumor cells, as in white matter tract.
Risk stratification in middle‐aged patients with congestive heart failure: prospective comparison of the Heart Failure Survival Score (HFSS) and a simplified two‐variable model
Authors: Christian Zugck, Carsten Krüger, Robert Kell, Sven Körber, Dieter Schellberg, Wolfgang Kübler, Markus Haass
Journal: European Journal of Heart Failure (2001)
Altered Calcium Handling Is Critically Involved in the Cardiotoxic Effects of Chronic β-Adrenergic Stimulation
Authors: Stefan Engelhardt, Lutz Hein, Vitaly Dyachenkow, Evangelia G. Kranias, Gerrit Isenberg, Martin J. Lohse
Journal: Circulation (2004)

Chronic adrenergic stimulation leads to cardiac hypertrophy and heart failure in experimental models and contributes to the progression of heart failure in humans. The pathways mediating the detrimental effects of chronic beta-adrenergic stimulation are only partly understood. We investigated whether genetic modification of calcium handling through deletion of phospholamban in mice would affect the development of heart failure in mice with transgenic overexpression of the beta1-adrenergic receptor.We crossed beta1-adrenergic receptor transgenic (beta1TG) mice with mice homozygous for a targeted deletion of the phospholamban gene (PLB-/-). Phospholamban ablation dramatically enhanced survival of beta1TG mice. The decrease of left ventricular contractility typically observed in beta1TG mice was reverted back to normal by phospholamban ablation. Cardiac hypertrophy and fibrosis were significantly inhibited in beta1TG/PLB-/- mice compared with beta1TG mice, and the heart failure-specific gene expression pattern was normalized. Analysis of intracellular calcium transients revealed increased diastolic calcium levels and decreased rate constants of diastolic calcium decline in beta1TG mice. In beta1TG/PLB-/- mice, diastolic calcium concentration was normal and rate constants of diastolic calcium decline were greater than in wild-type mice.We conclude that modification of abnormal calcium handling in beta1TG mice through ablation of phospholamban resulted in a rescue of functional, morphological, and molecular characteristics of heart failure in beta1-adrenergic receptor-transgenic mice. These results imply altered calcium handling as critical for the detrimental effects of beta1-adrenergic signaling.
The single-breath transfer factor for carbon monoxide and respiratory symptoms in a Norwegian community sample
Authors: I Welle, GE Eide, PS Bakke, A Gulsvik
Journal: European Respiratory Journal (1999)

Reduced single-breath transfer factors of the lung for carbon monoxide are seen in a number of conditions. The hypothesis of the present study was that self-reported respiratory symptoms differ in their prediction of TL,CO level in a general population in Norway. A cross-sectional survey of a general population sample in Norway, made up of 1,275 subjects aged 18-73 yrs, was conducted in 1987-1988. The attendees (84% response rate) filled in a questionnaire on respiratory symptoms and underwent standardized spirometric and TL,CO measurements and clinical examination. Associations between TL,CO and respiratory symptoms were assessed using multiple regression models. Tests for interaction were used to examine whether these associations varied with sex, age and smoking habits. Data from 1,221 subjects were analysed. Both males and females who reported respiratory symptoms had significantly lower TL,CO after adjusting for age and height. In a multiple linear regression analysis of TL,CO, adjusting for sex, age, height and smoking habits, the symptoms for which statistical significance was attained, were morning cough, chronic cough and breathlessness. However, only the breathlessness score was independently associated with the TL,CO (-0.42 mmol x min(-1) x kPa(-1) per breathlessness score unit) after adjusting for other respiratory symptoms, and the relationship was stronger in males than in females. In this study, the strongest predictor for a decreased single-breath transfer factor of the lung for carbon monoxide was the presence of self-reported breathlessness, regardless of age, smoking habits and height.
<i>Ex vivo</i>Culture with Interleukin (IL)-12 Improves CD8+ T-Cell Adoptive Immunotherapy for Murine Leukemia Independent of IL-18 or IFN-γ but Requires Perforin
Authors: Jennifer N. MacGregor, Qiao Li, Alfred E. Chang, Thomas M. Braun, Dennis P.M. Hughes, Kevin T. McDonagh
Journal: Cancer Research (2006)

Abstract In animal models and clinical trials, adoptive transfer of activated, antigen-specific CD8+ T cells mediates tumor regression in a cell dose-dependent manner. The cytokine interleukin (IL)-12 promotes CD8+ T-cell cytotoxicity and, with IL-18, synergistically up-regulates IFN-γ release. We have shown that culturing CD8+ T cells ex vivo with IL-12 and IL-18 enhanced antitumor responses in vivo and in vitro using a model of C1498/ovalbumin, a murine acute myeloid leukemia cell line expressing the antigen ovalbumin. Activated ovalbumin-specific CD8+ T cells cultured with IL-12, IL-18, both, or neither were assayed for antigen-specific cytokine production and cytolytic activity and adoptively transferred to C57BL/6 mice with established tumors. Maximal IFN-γ release occurred after T-cell culture with IL-12 and IL-18. Tumor-specific in vitro cytotoxicity was enhanced by IL-12, unaffected by addition of IL-18, and abrogated in perforin-deficient T cells irrespective of cytokine exposure. T cells cultured with IL-12 more effectively eliminated tumors, and addition of IL-18 did not further augment responses. IFN-γ-deficient CD8+ T cells showed effective antitumor activity that was enhanced by IL-12 with or without IL-18. Perforin-deficient CD8+ T cells were poor mediators of antitumor activity, though, and showed no improvement after culture with IL-12 and/or IL-18. Thus, ex vivo culture with IL-12 was sufficient to augment antigen-specific in vitro cytotoxicity and antitumor activity in vivo in an IFN-γ-independent but perforin-dependent manner. Ex vivo culture with IL-12 may improve CD8+ T-cell immunotherapy of cancer in the absence of donor cell–derived IFN-γ via perforin-mediated cytolysis. (Cancer Res 2006; 66(9): 4913-21)
The Foundling Museum
Authors: Joanna Lyall
Journal: BMJ (2004)

40 Brunswick Square, London WC1N 1AZ http://www.foundlingmuseum.org.uk/ Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Stigma, separation, segregation, and loss—the Foundling Museum, which opened in London's Bloomsbury last month, tells a sad tale. How could it be otherwise? Among the most affecting objects are the small tokens mothers attached to their babies when they left them to the care of the Foundling Hospital, hoping one day to reclaim the children they could not support. Between its inception in 1741 and its closure in 1953 the hospital, founded by the childless philanthropist Thomas Coram, looked after 27 000 deserted children. Admitted when they were under a year, babies were baptised by the hospital, given a new name, put out to a wet nurse or foster mother, and then readmitted between the ages of three and six and cared for until they were 21. Only a few were ever reclaimed by their mothers. [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Prolife Perinatologist — Paradox or Possibility?
Authors: John M. Thorp, Watson A. Bowes
Journal: New England Journal of Medicine (1992)

Is it possible to specialize in maternalfetal medicine without being willing to perform abortions? Or, to put it another way, is there such a thing as a prolife perinatologist?There are essentially two ethical positions with regard to the moral status of the embryo or fetus. One school of thought holds that human life begins at conception and that the embryo or fetus is a moral individual worthy of the protection society affords neonates. Such thinking is commonly labeled "antiabortion" or "prolife," and its proponents oppose any medical procedure that would interrupt pregnancy. The other school of thought maintains that . . .
Mortality within 24 hours of thrombolysis for myocardial infarction. The importance of early reperfusion. The GUSTO Investigators, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.
Authors: N S Kleiman, H D White, E M Ohman, A M Ross, L H Woodlief, R M Califf, D R Holmes, E Bates, M Pfisterer, A Vahanian
Journal: Circulation (1994)

BACKGROUND A paradoxical increased risk of death has been reported during the first 24 hours after thrombolysis for myocardial infarction. The mechanism of this phenomenon is not known, nor is its relation to the success or failure of reperfusion. The present study was a prospectively designed analysis of deaths occurring within the first 24 hours in the GUSTO trial. METHODS AND RESULTS There were 41,021 patients enrolled in GUSTO, a randomized comparison of streptokinase with intravenous or subcutaneous heparin, accelerated tissue-type plasminogen activator (TPA), and combination of streptokinase and TPA. An angiographic mechanistic substudy examined reperfusion (using the TIMI flow grading criteria) 90 minutes after the assigned thrombolytic regimen was begun in 1567 patients. There were 1125 deaths (2.8%) within 24 hours ("early deaths") and 1726 additional deaths (4.2%) after 24 hours but within 30 days ("later deaths"). At the time of presentation, the most potent predictors of early death were hypotension and sinus tachycardia. In a multiple logistic regression model, lower systolic blood pressure, shorter height, higher heart rate, and the absence of prior smoking distinguished early death from later death. Reinfarction occurred in 26 patients (2.4%), shock in 572 patients (52%), atrioventricular block in 308 patients (28%), and tamponade in 106 patients (10%) dying early compared with 262 (15%), 788 (46%), 396 (23%), and 74 (4%) respective patients dying later. There were no differences in early mortality among the thrombolytic regimens for the first 6 hours after randomization. By 24 hours, however, mortality was 2.89% for streptokinase recipients, 2.84% for combination therapy recipients, and 2.36% for accelerated TPA recipients (P = .005). There was little difference among patients with differing flow grades in the infarct artery during the first 4 hours, although mortality was 2.35% for patients with flow grade 0 or 1, 2.92% for patients with flow grade 2, and 0.89% for patients with flow grade 3. CONCLUSIONS Even with aggressive management regimens, mortality within the first 24 hours accounted for a large proportion of postthrombolytic deaths. Patients dying early were more likely to present with pump failure than were those dying later and were more likely to diet of events related to left ventricular dysfunction, although cardiac tamponade also accounted for a significant minority of these deaths. Thus, the severity of the clinical presentation rather than the underlying risk factors predicts early mortality. Based on the angiographic substudy data, it appears that rather than hastening early mortality, successful restoration of complete antegrade flow in the infarct-related artery protects against early death.
The impact on coagulation of an intravenous loading dose in addition to a subcutaneousregimen of low-molecular-weight heparinin the initial treatment of acute coronary syndromes
Authors: Nick R Bijsterveld, Arno H Moons, Joost C.M Meijers, Marcel Levi, Harry R Büller, Ron J.G Peters
Journal: Journal of the American College of Cardiology (2003)
Comparison of serum oestrogen concentrations in post-menopausal women taking oestrone sulphate and oestradiol.
Authors: A B Anderson, E Sklovsky, L Sayers, P A Steele, A C Turnbull
Journal: BMJ (1978)

Mean serum concentrations of oestradiol-17beta, oestrone, and oestrone sulphate in postmenopausal women were the same when measured up to six hours after treatment with either piperazine oestrone sulphate 1.5 mg or oestradiol valerate 2 mg. Maximum concentrations of oestradiol were less than those of oestrone, but oestrone sulphate reached concentrations about 30 times higher than those of oestrone. The rapid conversion of oestradiol valerate to oestrone and oestrone sulphate does not support the suggestion that in menopausal women oestradiol is less likely to be associated with a risk of endometrial carcinoma than oestrone sulphate, since the two preparations appear to become identical after ingestion.
Henderson and Gillespie's Textbook of Psychiatry: For Students and Practitioners
Authors: Paul G. Myerson
Journal: JAMA (1969)

Sir David Henderson, who died in 1965 at the age of 81 years, had written the greater part of the original edition as well as its subsequent eight editions over a period of 35 years, Dr. Ivor R. C. Batchelor, who is professor of psychiatry at the University of Dundee, has revised and added chapters to the present edition "to deal more fully with current interests and problems." Dr. Batchelor's eclecticism has led him to cover a wide range of topics, probably too wide to be entirely relevant to most students and practitioners for whom the book is intended—eg, why a chapter on epilepsy in a textbook on psychiatry? His broadminded point of view, in the tradition of most textbooks of psychiatry, is more balanced than integrated and it does not capture the flavor of the psychiatry of the 1960's which, as I think Grinker once put it, has been
PHYSIOLOGY AND MODERN SURGERY
Authors: J. SHELTON HORSLEY
Journal: JAMA (1928)

A surgeon, like a practitioner of any branch of medicine, is in a sense a biologist, for he is dealing with living tissue. The mechanical features of surgery have often been too much glorified. They are, to be sure, important, but a knowledge of the physiologic processes in the human body is equally essential. A patient who dies because the surgeon transplanted the ureters into the small intestine, where absorption is rapid, instead of into the rectum or sigmoid, whose function is chiefly receptacular, is just as dead as one who succumbs because of a defective intestinal suture or a poorly tied blood vessel. Successful surgery does not mean just the skilful mechanical performance of an operation. It is something even more important than this. It involves the consciousness of the surgeon that the technical steps are not an end in themselves but are more or less important guides toward