tbuckley/cabot-search huggingface dataset:
THE OCCURRENCE OF DEGRADED PNEUMOCOCCI IN VIVO
Authors: Hobart A. Reimann
Journal: The Journal of Experimental Medicine (1927)

It is conceivable that a change from the virulent, non-phagocytable S form of Pneumococcus to the avirulent phagocytable R form may take place in pneumococcus disease, but the experiments here reported do not settle the question whether or not this is an important factor in determining the outcome in natural infection. It has been shown experimentally that the degradation from the S form to the R form actually does take place in cultures of Pneumococcus growing in agar subcutaneously embedded in guinea pigs, in agar enclosed in vials subcutaneously embedded in rabbits, and spontaneously in the blood stream of infected horses. However, it was not possible in any of the experiments here cited to demonstrate the complete change from S to R pneumococci before the bacteria disappeared from the body. When the intermediate or R forms did appear, they were always accompanied and usually exceeded in number by the S forms and all three forms disappeared together. S organisms may disappear entirely without evidence of first going through the intermediate and R stages. On the other hand, contrary to expectations, pure cultures of R forms remained viable in subcutaneous foci for weeks although apparently freely accessible to the action of phagocytes. It seems of some significance that the R forms appeared early in the vials (inoculated with S pneumococci) in immunized and normal rabbits alike, indicating that the presence of demonstrable specific immune bodies was not alone responsible for the variation of the bacteria. Of some importance also is the fact that R forms were never derived from similarly prepared control cultures growing in vitro at the same temperature and immersed in normal serum, although the S forms remained viable and unaltered for 6 weeks. It is likely that variations of pneumococci do not occur readily when S cultures are exposed to normal serum in vitro, especially when growing in closed vials under a diminished oxygen supply, for it has previously been shown (2) that only slight variation occurs even after prolonged (240) transfers in heterologous serum broth in the test-tube. It is possible, therefore, that the variation which occurred among pneumococci growing in agar vials embedded in normal rabbits was actually provoked by unknown influences in the living tissue fluids. Although R forms have been shown to occur in vivo, no positive evidence can be derived from these experiments to prove that recovery from pneumococcus infection depends upon the degradation of the virulent S forms of pneumococci to the avirulent R forms and the subsequent destruction of the latter by phagocytes.
Medical Care in the People's Republic of China: Access and Cost
Authors: MYRON S. COHEN
Journal: Annals of Internal Medicine (1983)

It is important, when considering the impact of the Chinese health care model, on developing countries, to reexamine this system as China heightens its drive toward modernization. 2 questions about the system are the concern of this report: how good is access to tertiary care; and what is the cost of this care. To gain information on access of patients to the health care system, the pattern of admissions during a 3-month period of all patients to an infectious disease ward were studied. A well established referral pattern was used by the hospitals to send patients to higher levels of care. The distance to tertiary care centers, as well as limited transportation available, leads to more frequent use of tertiary care centers by urban rather than rural populations. Ironically, many patients are simply too sick to travel to more elaborate facilities. Although policies discourage the use of higher level facilities, Chinese patients (particularly those in urban areas), used various strategies to gain access to facilities that they thought would best serve their needs. Insurance reimbursement policies may discourage rural patients from seeking admission to tertiary care facilities. The cost of health care in the ward was analyzed by studying records from randomly selected patients. Hospital bills differed greatly, and the overall cost of hospitalization was markedly affected by duration and the use of medications. In sharp contrasts to US hospitals, diagnostic testing had only a minor effect on costs, primarily because of limited availability of equipment and circumspect use of resources. At no time was "defensive medicine" as in the use of laboratory or roentgenographic testing observed. Medications, the largest portion of a patient's charges, were used freely even in situations without documented efficacy. The average cost of hospitalization was $119, but at the time of this study, the average Chinese citizen earned approximately $250 per year. Marked differences between regions and sectors persisted, and the ratio in per capita income between urban and rural populations was estimated at 3 to 1. For most city workers and government employees, health care costs are completely covered by work units, if the patient's care is delivered according to the appropriate referral channels. Among rural peasants, 80% of the population, the amount of insurance coverage depends on the financial stability of the commune, and reimbursement may represent as little as 50% of patient charges. 1 of the most important questions facing health care planners in China is the way the system will be modernized and resources properly distributed.
Molecular strategies for detection and quantitation of clonal cytotoxic T-cell responses in aplastic anemia and myelodysplastic syndrome
Authors: Marcin W. Wlodarski, Lukasz P. Gondek, Zachary P. Nearman, Magdalena Plasilova, Matt Kalaycio, Eric D. Hsi, Jaroslaw P. Maciejewski
Journal: Blood (2006)
Therapy of severe diabetic ketoacidosis. Zero-mortality under very-low-dose insulin application.
Authors: A Wagner, A Risse, H L Brill, V Wienhausen-Wilke, M Rottmann, K Sondern, B Angelkort
Journal: Diabetes Care (1999)

OBJECTIVE: Despite modern concepts in therapy by low-dose insulin application and better care in intensive care units (ICUs), there still is a mortality of 5-10% for severe diabetic ketoacidosis (DKA). The aim of this study was to develop a therapy concept to reduce complications and mortality in DKA. RESEARCH DESIGN AND METHODS: From 1986 to 1997, 114 consecutive patients (mean [range]; age 34 [11-74] years) with type 1 diabetes suffering from severe DKA were treated on ICUs and investigated in a retrospective and prospective study. The following are the criteria for admission onto ICUs: &amp;lt; 7.20 pH level, &amp;gt; 300 mg/dl blood glucose, less than -12 mmol/l base excess, or &amp;lt; 300 mg/dl blood glucose plus severe symptoms (i.e., coma). We treated patients according to the following concepts: very-low-dose insulin application by a basal insulin infusion of 1 U/h (0.5-4.0 U/h i.v.), maximal decrease of blood glucose level by 50 mg. dl-1. h-1, slow-motion reequilibration by fluid substitution of 1,000 ml/h (Ringer-Lactate, NaCl 0.9% or half-electrolyte fluids) in the first 4 h, potassium replacement and heparin (500-1,000 U/h i.v.). RESULTS: When patients were admitted to ICU, we found the following parameters: mean (range); 609.0 (86.0-1,428.0) mg/dl blood glucose level; 7.13 (6.53-7.36) pH level; and -19.7 (-41.2 to -7.0) mmol/l base excess. After 12 h of treatment, we reached the following parameters: mean values; 251 mg/dl blood glucose level, 7.31 pH level, and -9.37 mmol/l base excess level. All patients survived without any lasting deficiencies or fatal complications. CONCLUSIONS: Very-low-dose insulin application and slow-motion reequilibration plus monitored substitution of electrolytes are the basic strategies in the treatment of severe DKA. In our view, small doses of infused insulin are the main reason for the safe results of this therapy program.
Operative and Middle-Term Results of Cardiac Surgery in Nonagenarians
Authors: Giuseppe Speziale, Giuseppe Nasso, Maria Cristina Barattoni, Raffaele Bonifazi, Giampiero Esposito, Roberto Coppola, Georges Popoff, Mauro Lamarra, Marcio Scorcin, Ernesto Greco, Vincenzo Argano, Claudio Zussa, Donald Cristell, Francesco Bartolomucci, Luigi Tavazzi
Journal: Circulation (2010)

Age >90 years represents in many centers an absolute contraindication to cardiac surgery. Nonagenarians are a rapidly growing subset of the population posing an expanding clinical problem. To provide helpful information in regard to this complex decision, we analyzed the operative and 5-year results of coronary and valvular surgical procedures in these patients.We retrospectively reviewed 127 patients aged >or=90 years who underwent cardiac surgery within our hospital group in the period 1998 to 2008. Kaplan-Meier and multiple logistic regression analyses were performed. A longer follow-up than most published studies and the largest series published thus far are presented. Mean age was 92 years (range, 90 to 103 years). Mean logistic EuroSCORE was 21.3+/-6.1. Sixty patients had valvular surgery (including 11 valve repairs), 49 patients had coronary artery bypass grafting, and 18 had valvular plus coronary artery bypass grafting surgery (55 left mammary artery grafts implanted). Forty-five patients (35.4%) were operated on nonelectively. Operative mortality was 13.4% (17 cases). Fifty-four patients (42.5%) had a complicated postoperative course. There were no statistically significant differences in the rate and type of complications between patient strata on the basis of type of surgery performed. Nonelective priority predicted a complicated postoperative course. Predictors of operative mortality were nonelective priority and previous myocardial infarction. Kaplan-Meier survival estimates at 5 years were comparable between patient groups on the basis of procedure performed.Although the rate of postoperative complications remains high, cardiac surgery in nonagenarians can achieve functional improvement at the price of considerable operative and follow-up mortality rates. Cardiac operations in these very elderly subjects are supported if appropriate selection is made and if the operation is performed earlier and electively. Our results should contribute to the development of guidelines for cardiac operations in nonagenarians.
Increased Immunoreactive Endothelin-1 in Human Transplant Coronary Artery Disease
Authors: Stefano Ravalli, Matthias Szabolcs, Arline Albala, Robert E. Michler, Paul J. Cannon
Journal: Circulation (1996)

Background The pathogenesis of transplant coronary artery disease (TCAD) is unknown, but it is thought to derive from an interaction between immune and nonimmune factors, leading to smooth muscle cell proliferation and accumulation in the expanded neointima. Endothelin-1 (ET-1), a potent vasoconstrictor with mitogenic properties for vascular smooth muscle cells, has recently been demonstrated in native vessel atherosclerosis. The present study used immunohistochemistry to investigate the role of ET-1 in TCAD. Methods and Results ET-1 immunoreactivity and cellular localization were assessed in human coronary arteries with TCAD (n=13) and in normal coronary arteries (n=10) with single- and double-label immunohistochemistry. The intensity of immunostaining was determined by a semiquantitative method. Diffuse and intense ET-1 immunoreactivity was found in 11 of 13 patients with TCAD (85%), mainly in myointimal cells and, in lesser amounts, in macrophages and endothelial cells. In contrast, normal coronary arteries had only faint immunostaining localized to the endothelial layer. Mean semiquantitative grade was significantly higher in TCAD than in normal arteries (1.8 versus 0.7; P &lt;.05). ET-1 was more frequently present in lipid-rich, atheromatous lesions than in lipid-poor, proliferative ones. Intimal neovessels consistently immunostained for ET-1. Conclusions Immunoreactivity for ET-1 is significantly increased in TCAD, possibly as a result of stimulatory cytokines and growth factors that are upregulated in the posttransplant state. The results suggest a role for this mitogenic peptide in the pathogenesis of graft arteriosclerosis.
Spain takes tough stance on smoking with new legislation
Authors: A. G. Rada
Journal: BMJ (2010)

A total ban on smoking in enclosed public places and outside health centres, schools, and children’s playgrounds could take effect in Spain early next year if draft legislation becomes law.

The passing of the legislation by Spain’s lower house of parliament, the Congress of Deputies, on 20 October is seen as a victory for antismoking campaigners, who have had to fight off strong pressure from Spain’s tobacco lobby. The ruling party, the centre left Socialist Workers’ Party (PSOE), also resisted pressure from the opposition conservative Popular Party, which has opposed a full ban because of the alleged economic effects on the hotel and catering industry.

A loophole in the present law, which was introduced in 2006, exempts certain bars and restaurants …
THE POSTTRAUMATIC NEUROSES
Authors: GEORGE W. HALL
Journal: JAMA (1934)

One of the oldest questions which trouble the mind of the physician is that pertaining to those frequent and baffling nervous states following trauma. The number and importance of these conditions seem to be increasing with the widespread use of machinery in modern industry and transportation. No physician can escape these cases, and all are daily impressed with the great loss of time and money, both to the employer and to the patient, which they bring about. An age-old conflict is being waged today, as in years gone by, between the exponents of the so-called organic and functional interpretations of these conditions. Before the day of Charcot, the explanation was usually sought in organic disturbances of the nervous system, but this great French neurologist early recognized the potent rôle played by emotional factors. The earliest work of Sigmund Freud, while a student of Charcot's, was in connection with patients exhibiting
Treatment of myocardial infarction
Authors: M D Stevenson
Journal: BMJ (1995)

strategies but have little or no leverage with general practice fundholders to implement them.The emphasis on general practice fundholders as purchasers is a move away from population based purchasing, which took into account the major influences on health.'It is not clear how a local population perspective of health and health care needs developed by health authorities will be able to influence general practice fimdholders.Furthermore, if health authorities are to become the new "regulators" of general practice fundholders4 all their resources will be taken up with this time consuming task, which will increase the transaction costs inherent in the internal market.
Panel needed to combat research fraud
Authors: B. Christie
Journal: BMJ (1999)

A national panel is needed in Britain to provide advice and assistance on dealing with the problem of misconduct in biomedical research, a consensus conference has concluded.

The conference called for a meeting to be held between the General Medical Council, the three royal colleges of physicians, and the Faculty of Pharmaceutical Medicine to determine the precise role of the proposed new body.

The two day conference, held at the Royal College of Physicians of …
Editor Journal American Medical Association
Authors: C. Hixson
Journal: JAMA (1883)

Having been for twenty-five years a victim of hay-fever, and having been compelled to suffer all the torments of this disease, sitting in a chair for sixteen consecutive nights in order to get a modicum of sleep and rest, and having ransacked the whole literature of hay-fever as known in the English language, as far as I could obtain it, I am, as you may well imagine, much interested in anything that appertains to this inscrutable and abominable disease. No living man, who is not a victim, can appreciate the agony of hay-fever. Allow me to say that so far as twenty-five years can give a man authority to speak, I say that it is my opinion that no remedy has as yet been found; no, not so much as even a palliative for genuine hay-fever. For the last twenty-five years half of the materia medica has either gone through
Tainted Infant Formula
Authors: Joan Stephenson
Journal: JAMA (2008)

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Abstract B88: Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination
Authors: Sara I. Cunha
Journal: Cancer Research (2013)

Abstract Therapy-induced resistance remains a significant hurdle to achieve long-lasting responses and cures in cancer patients. Here, we investigated the long-term consequences of genetically impaired angiogenesis by engineering multiple tumor models deprived of endoglin, a co-receptor for TGF-beta in endothelial cells actively engaged in angiogenesis. Tumors from endoglin-deficient mice adapted to the weakened angiogenic response and refractoriness to diminished endoglin signaling was accompanied by increased metastatic capability. Mechanistic studies in multiple mouse models of cancer revealed that deficiency for endoglin resulted in a tumor vasculature that displayed hallmarks of endothelial-to-mesenchymal transition; a process of previously unknown significance in cancer biology, but here shown to be associated with a reduced capacity of the vasculature to avert tumor cell intra- and extravasation. Nevertheless, tumors deprived of endoglin exhibited a delayed onset of resistance to anti-VEGF agents, illustrating the therapeutic utility of combinatorial targeting of multiple angiogenic pathways for the treatment of cancer. Citation Format: Sara I. Cunha. Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B88.
Antitumor Efficacy of the Novel RAF Inhibitor GDC-0879 Is Predicted by BRAFV600E Mutational Status and Sustained Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Pathway Suppression
Authors: Klaus P. Hoeflich, Sylvia Herter, Janet Tien, Leo Wong, Leanne Berry, Jocelyn Chan, Carol O'Brien, Zora Modrusan, Somasekar Seshagiri, Mark Lackner, Howard Stern, Edna Choo, Lesley Murray, Lori S. Friedman, Marcia Belvin
Journal: Cancer Research (2009)

Oncogenic activation of the BRAF serine/threonine kinase has been associated with initiation and maintenance of melanoma tumors. As such, development of pharmacologic agents to target RAF proteins or their effector kinases is an area of intense investigation. Here we report the biological properties of GDC-0879, a highly selective, potent, and orally bioavailable RAF small-molecule inhibitor. We used extracellular signal-regulated kinase (ERK)-1/2 and mitogen-activated protein kinase/ERK kinase (MEK)-1/2 phosphorylation as biomarkers to explore the relationship between tumor outcome and pharmacodynamic inhibition of the RAF-MEK-ERK pathway. In GDC-0879-treated mice, both cell line- and patient-derived BRAF(V600E) tumors exhibited stronger and more sustained pharmacodynamic inhibition (>90% for 8 hours) and improved survival compared with mutant KRAS-expressing tumors. Despite the involvement of activated RAF signaling in RAS-induced tumorigenesis, decreased time to progression was observed for some KRAS-mutant tumors following GDC-0879 administration. Moreover, striking differences were noted for RAF and MEK inhibition across a panel of 130 tumor cell lines. Whereas GDC-0879-mediated efficacy was associated strictly with BRAF(V600E) status, MEK inhibition also attenuated proliferation and tumor growth of cell lines expressing wild-type BRAF (81% KRAS mutant, 38% KRAS wild type). The responsiveness of BRAF(V600E) melanoma cells to GDC-0879 could be dramatically altered by pharmacologic and genetic modulation of phosphatidylinositol 3-kinase pathway activity. These data suggest that GDC-0879-induced signaling changes are dependent on the point of oncogenic activation within the RAS network. Taken together, these studies increase our understanding of the molecular determinants for antitumor efficacy resulting from RAF pathway inhibition and have implications for therapeutic intervention in the clinic.
FLOW REGULATOR FOR INTRAVENOUSLY ADMINISTERED FLUIDS
Authors: Boyd L. Mahuron
Journal: JAMA (1952)

<h3>To the Editor:</h3> —In regard to the flow regulator for intravenously administered fluids, described by Dr. Feldman inThe Journal(<b>149</b>:1017 [July 12] 1952), I would like to suggest that Dr. Feldman's clamp be made with the projection between the thumbscrews of the movable bar as shown in the accompanying diagram (front and side views of simplified clamp). Doing this would permit both thumbscrews to turn in the same direction to regulate the flow. As originally shown, they would have to be turned in opposite directions to accomplish the desired coarse and fine adjustments. It is also suggested that right hand threads be used on the thumbscrews as shown here instead of left hand threads as shown in the original diagram. The simplified clamp permits turning thumbscrew B (coarse adjustment) and thumbscrew A (fine adjustment) in the same direction to accomplish the desired change of pressure on the tubing
Circulatory Effects of Salicylates
Authors: R. P. WALTON, T. D. DARBY
Journal: Circulation Research (1958)

Sodium salicylate consistently produces a prompt increase in heart contractile force when injected in anesthetized dogs in doses of 100 mg./Kg. intravenously. The increase in force is about 30 per cent and declines to control levels in 15 to 20 min. This effect is not considered of important therapeutic significance. Total doses of about 400 mg./Kg. consistently produce marked hyperpyrexia which closely resembles that of dinitrophenol and applied external heat in its circulatory characteristics; conspicuous features are extreme tachycardia, depressed S-T segment, moderate increase in heart force, and aortic pulse contours which indicate reduced stroke volume and vasodilation.