tbuckley/cabot-search huggingface dataset:
THE TRANSMISSION OF YELLOW FEVER.
Authors: JAMES CARROLL
Journal: JAMA (1903)

Several American observers have noted that during the yellow fever outbreaks mosquitoes were very numerous, among them Bush,<sup>1</sup>at Philadelphia in 1797; Dr. Weightman,<sup>2</sup>of the U. S. Army, at St. Augustine, Fla., in 1839; Dr. Wood,<sup>3</sup>at Centerville, Miss., in 1853. Dr. E. H. Barton<sup>3</sup>states "that at Clinton, La., in 1853, mosquitoes were uncommonly numerous night and day." At Trinity, La., in the same year, when sawdust was used to fill up low places in the streets, the disease was not propagated, though many cases were brought there and no precautions were used.<sup>3</sup>It is hardly necessary to note what the effect of this obliteration of puddles would be on the development of mosquitoes. Dr. Beyrenheidt<sup>3</sup>of Biloxi, Miss., in reporting a severe epidemic at that place in 1853, during which 533 cases and 111 deaths occurred in a population of 5,520, makes the interesting statement that
Provision of health advice for UK medical students planning to travel overseas for their elective study period: questionnaire survey
Authors: P. J Moss, N. J Beeching
Journal: BMJ (1999)

An external elective period is included in the curriculum of most medical schools in the United Kingdom.Of this year's applicants for elective grants at one school, 97% planned to go abroad; 69% of applicants chose developing countries, the most popular destination being southern Africa.Attention has been drawn to the potential health risks facing elective students (J H Cossar et al, fifth international conference on travel medicine, 1995 (abstract 201)) and also to the risk of HIV infection for health workers in developing countries. 1We conducted a survey to determine how health advice for elective students who plan to travel abroad is provided. Methods and resultsWe sent a questionnaire to the 26 medical schools in the United Kingdom after making a telephone call to determine the most appropriate addressee.A telephone reminder was made to those who had not responded after four weeks.Further detail about the questionnaire is on the BMJ's website.Twenty two replies (85%) were received (table).Of the medical schools from which no response had been received, two stated at the reminder call that the addressee was on leave and two that the form would be returned soon.Most medical schools (20) that replied provided some form of travel health advice, usually in the form of a group lecture or seminar.Some distributed written guidance: this ranged from a single paragraph about health in a document covering various elective issues, to a comprehensive 12 page guide to travel and occupational health.Few schools (7) made internal provision for immunisations, and many of those that did not make such provision also had no check on whether students had followed the advice given.Only 2 schools offered routine health screening to elective students on their return.Almost all the respondents (21) said that students were given advice about HIV infection.In many cases, however, this was as part of the normal curriculum, and academic knowledge concerning HIV infection and AIDS in Britain does not necessarily correlate with an understanding of the personal risks involved in working in the developing world.Most schools had not considered how current guidelines for the management of occupational exposure to HIV could be applied to overseas elective students. 2
Novel self assembling nanoparticles for the oral administration of fondaparinux: Synthesis, characterization and in vivo evaluation
Authors: Bettina Ralay-Ranaivo, Didier Desmaële, Elsa P. Bianchini, Elise Lepeltier, Claudie Bourgaux, Delphine Borgel, Thierry Pouget, Jean François Tranchant, Patrick Couvreur, Ruxandra Gref
Journal: Journal of Controlled Release (2014)

Fondaparinux (Fpx) is the anticoagulant of choice in the treatment of short- and medium-term thromboembolic disease. To overcome the low oral bioavailability of Fpx, a new nanoparticulate carrier has been developed. The nanoparticles (NPs) contain squalenyl derivatives, known for their excellent oral bioavailability. They spontaneously self-assemble upon both electrostatic and hydrophobic interactions between the polyanionic Fpx and cationic squalenyl (CSq) derivatives. The preparation conditions were optimized to obtain monodisperse, stable NPs with a mean diameter in the range of 150–200 nm. The encapsulation efficiencies were around 80%. Fpx loadings reached 39 wt.%. According to structural and morphological analysis, Fpx and CSq organized in spherical multilamellar ("onion-type") nanoparticles. Furthermore, in vivo studies in rats suggested that Fpx was well absorbed from the orally administered NPs, which totally dissociated when reaching the blood stream, leading to the release of free Fpx. The Fpx:CSq NPs improved the plasmatic concentration of Fpx in a dose-dependent manner. However, the oral bioavailability of these new NPs remained low (around 0.3%) but of note, the Cmax obtained after oral administration of 50 mg/kg NPs was close to the prophylactic plasma concentration needed to treat venous thromboembolism. Moreover, the oral bioavailability of Fpx could be dramatically increased up to 9% by including the nanoparticles into gastroresistant capsules. This study opens up new perspectives for the oral administration of Fpx and paves the way towards elaborating squalene-based NPs which self assemble without the need of covalently grafting the drug to Sq.
Adjustable, Physiological Ventricular Restraint Improves Left Ventricular Mechanics and Reduces Dilatation in an Ovine Model of Chronic Heart Failure
Authors: Ravi K. Ghanta, Aravind Rangaraj, Ramanan Umakanthan, Lawrence Lee, Rita G. Laurence, John A. Fox, R. Morton Bolman, Lawrence H. Cohn, Frederick Y. Chen
Journal: Circulation (2007)

Background— Ventricular restraint is a nontransplantation surgical treatment for heart failure. The effect of varying restraint level on left ventricular (LV) mechanics and remodeling is not known. We hypothesized that restraint level may affect therapy efficacy. Methods and Results— We studied the immediate effect of varying restraint levels in an ovine heart failure model. We then studied the long-term effect of restraint applied over a 2-month period. Restraint level was quantified by use of fluid-filled epicardial balloons placed around the ventricles and measurement of balloon luminal pressure at end diastole. At 4 different restraint levels (0, 3, 5, and 8 mm Hg), transmural myocardial pressure (P tm ) and indices of myocardial oxygen consumption (MV̇ o 2 ) were determined in control (n=5) and ovine heart failure (n=5). Ventricular restraint therapy decreased P tm and MV̇ o 2 , and improved mechanical efficiency. An optimal physiological restraint level of 3 mm Hg was identified to maximize improvement without an adverse affect on systemic hemodynamics. At this optimal level, end-diastolic P tm and MV̇ o 2 indices decreased by 27% and 20%, respectively. The serial longitudinal effects of optimized ventricular restraint were then evaluated in ovine heart failure with (n=3) and without (n=3) restraint over 2 months. Optimized ventricular restraint prevented and reversed pathological LV dilatation (130±22 mL to 91±18 mL) and improved LV ejection fraction (27±3% to 43±5%). Measured restraint level decreased over time as the LV became smaller, and reverse remodeling slowed. Conclusions— Ventricular restraint level affects the degree of decrease in P tm , the degree of decrease in MV̇ o 2 , and the rate of LV reverse remodeling. Periodic physiological adjustments of restraint level may be required for optimal restraint therapy efficacy.
Subclass restriction of murine antibodies. II. The IgG plaque-forming cell response to thymus-independent type 1 and type 2 antigens in normal mice and mice expressing an X-linked immunodeficiency.
Authors: J Slack, G P Der-Balian, M Nahm, J M Davie
Journal: The Journal of Experimental Medicine (1980)

Antigens have been classified previously into three categories, thymus-dependent (TD), thymus-independent type (TI) 1, and TI-2, based upon thymic dependence and ability to stimulate an immunodeficient strain of mouse, CBA/N. Here we demonstrate that the different antigen classes elicit IgG antibodies of different subclasses. TD antigens stimulate predominantly IgG1 antibodies, with smaller amounts of IgG2 and IgG3 being expressed. TI-1 antigens stimulate almost no IgG1 antibodies and equal amounts of IgG2 and IgG3. TI-2 antigens elicit predominantly IgG3 antibodies. Mice expressing the CBA/N phenotype are known to be nonresponsive to TI-2 antigens. This was confirmed in this study. In addition, we demonstrate that the IgG3 component of the response to TI-1 antigens is virtually absent in mice expressing the CBA/N phenotype, which supports our previous finding that the CBA/N defect may be restricted to a B-lymphocyte subpopulation containing most of the precursors of IgG3-secreting cells.
Anthony De Tomaso: Finding the origins of adaptive immunity
Authors: Anthony De Tomaso
Journal: The Journal of Experimental Medicine (2008)

Text and Interview by Hema Bashyam

As a student, Anthony De Tomaso was fascinated by many aspects of biology, from molecular biology to marine biology and development to immunology. Now as head of the same lab that he joined as a postdoctoral fellow, De Tomaso has marshaled his diverse scientific
THE CARE OF INFANTS IN PUBLIC INSTITUTIONS.
Authors: H. M. McCLANAHAN
Journal: JAMA (1905)

It has long been recognized that the care of infants in public institutions presents peculiar difficulties. The mortality is greater among these, in any given disease, than in private practice. The reason why the institution infant has less resisting power is, no doubt, because of its impaired nutrition; and faulty nutrition is probably the result of poor food, bad air and lack of maternal care. It can not fail to have been noticed by all doing hospital work that all infections are more severe among numbers, as in a ward, than among isolated individuals. The observations on which this paper is based were made in the Child's Saving Institution, Omaha, Neb., and covered a period of four years. This is an eleemosynary institution, supported by public-spirited citizens. It receives infants and children for care and adoption. During the years of 1902-3 the nursery was not in charge of a trained
VITAL CAPACITY OF NEGRO RACE
Authors: W. G. SMILLIE
Journal: JAMA (1926)

This study of the vital capacity of negroes is a by-product of a hookworm study in a group of about 2,000 white and negro children of school age, in south Alabama. These children were measured carefully to determine the effect of varying intensities of hookworm infection on normal growth and development.<sup>1</sup>One of the measurements used in the determination of the physical condition of these children was vital capacity. We were surprised to find that normal negro children had markedly lower vital capacity than white children of the same age, sex and economic status. The groups studied were children of school age (from 6 to 16 years) from the rural districts of Alabama. Their dietary contained sufficient calories but was badly balanced. The white families lived on little farms, side by side with the negroes and on a similar economic level. Hygienic conditions were similar in the two races.
Novel Properties of Tyrosine-mutant AAV2 Vectors in the Mouse Retina
Authors: Hilda Petrs-Silva, Astra Dinculescu, Qiuhong Li, Wen-Tao Deng, Ji-jing Pang, Seok-Hong Min, Vince Chiodo, Andy W Neeley, Lakshmanan Govindasamy, Antonette Bennett, Mavis Agbandje-McKenna, Li Zhong, Baozheng Li, Giridhara R Jayandharan, Arun Srivastava, Alfred S Lewin, William W Hauswirth
Journal: Molecular Therapy (2010)

Vectors based on adeno-associated virus serotype 2 (AAV2) have been used extensively in many gene-delivery applications, including several successful clinical trials for one type of Leber congenital amaurosis in the retina. Many studies have focused on improving AAV2 transduction efficiency and cellular specificity by genetically engineering its capsid. We have previously shown that vectors-containing single-point mutations of capsid surface tyrosines in serotypes AAV2, AAV8, and AAV9 displayed significantly increased transduction efficiency in the retina compared with their wild-type counterparts. In the present study, we evaluated the transduction characteristics of AAV2 vectors containing combinations of multiple tyrosine to phenylalanine mutations in seven highly conserved surface-exposed capsid tyrosine residues following subretinal or intravitreal delivery in adult mice. The multiply mutated vectors exhibited different in vivo transduction properties, with some having a unique ability of transgene expression in all retinal layers. Such novel vectors may be useful in developing valuable new therapeutic strategies for the treatment of many genetic diseases. Vectors based on adeno-associated virus serotype 2 (AAV2) have been used extensively in many gene-delivery applications, including several successful clinical trials for one type of Leber congenital amaurosis in the retina. Many studies have focused on improving AAV2 transduction efficiency and cellular specificity by genetically engineering its capsid. We have previously shown that vectors-containing single-point mutations of capsid surface tyrosines in serotypes AAV2, AAV8, and AAV9 displayed significantly increased transduction efficiency in the retina compared with their wild-type counterparts. In the present study, we evaluated the transduction characteristics of AAV2 vectors containing combinations of multiple tyrosine to phenylalanine mutations in seven highly conserved surface-exposed capsid tyrosine residues following subretinal or intravitreal delivery in adult mice. The multiply mutated vectors exhibited different in vivo transduction properties, with some having a unique ability of transgene expression in all retinal layers. Such novel vectors may be useful in developing valuable new therapeutic strategies for the treatment of many genetic diseases.
Response to Letter Regarding Article, “Cardiac Troponin I but Not Cardiac Troponin T Induces Severe Autoimmune Inflammation in the Myocardium”
Authors: Stefan Göser, Martin Andrassy, Sebastian J. Buss, Florian Leuschner, Christian H. Volz, Renate Öttl, Stefan E. Hardt, Hugo A. Katus, Ziya Kaya, Stefan Zittrich, Natascha Blaudeck, Gabriele Pfitzer, Noel R. Rose
Journal: Circulation (2007)

We thank Drs Conti and Volpe for their valuable comments regarding our article. 1We agree with their opinion that autoimmunity to troponins might have additional influence on the pathogenesis of cardiovascular diseases.In our recent publication, we describe how the induction of an immune response to troponin I (TnI) can induce a severe inflammation and fibrosis and then dilation and dysfunction of the myocardium.Furthermore, we show that preimmunization before the ligation of the left anterior descending artery leads to increased inflammation and ischemia-induced infarct size. 1 In our discussion, we mainly focus on the effects of inducing autoimmunity toward the myocardium, and we do not discuss the possible implications of our findings on the development of atherothrombosis.Our results demonstrate an important effect for inducing an autoimmune response against TnI (the preferred marker of myocardial damage and risk stratification in acute coronary syndrome) in heart failure.These findings may aid in developing new approaches to the early treatment of heart failure in some patients and initiating further (clinical) studies to investigate the role of TnI release during acute cardiac damage and induction of autoimmunity against TnI in postinfarct remodeling and its role in heart failure.Additionally, as Drs Conti and Volpe mention, it has recently been reported that increased levels of troponins can be found in patients without acute coronary syndrome and that these levels correlate to 10-year mortality. 2These results are supported by our recent findings that levels of increased antibody titers against TnI can be found not only in patients with acute coronary syndromes but also in some subjects without a known history for cardiovascular diseases (Z.Kaya, MD, unpublished data, 2006), where they also may be useful as predictors for future heart disease and mortality.In conclusion, we agree with Drs Conti and Volpe that more basic and clinical studies need to be performed to elucidate the role of autoimmunity to troponins as predictors of heart failure and atherothrombosis.
Cross-presenting CD103+ dendritic cells are protected from influenza virus infection
Authors: Julie Helft, Balaji Manicassamy, Pierre Guermonprez, Daigo Hashimoto, Aymeric Silvin, Judith Agudo, Brian D. Brown, Mirco Schmolke, Jennifer C. Miller, Marylene Leboeuf, Kenneth M. Murphy, Adolfo García-Sastre, Miriam Merad
Journal: Journal of Clinical Investigation (2012)

CD8+ cytotoxic T cells are critical for viral clearance from the lungs upon influenza virus infection. The contribution of antigen cross-presentation by DCs to the induction of anti-viral cytotoxic T cells remains controversial. Here, we used a recombinant influenza virus expressing a nonstructural 1–GFP (NS1-GFP) reporter gene to visualize the route of antigen presentation by lung DCs upon viral infection in mice. We found that lung CD103+ DCs were the only subset of cells that carried intact GFP protein to the draining LNs. Strikingly, lung migratory CD103+ DCs were not productively infected by influenza virus and thus were able to induce virus-specific CD8+ T cells through the cross-presentation of antigens from virally infected cells. We also observed that CD103+ DC resistance to infection correlates with an increased anti-viral state in these cells that is dependent on the expression of type I IFN receptor. These results show that efficient cross-priming by migratory lung DCs is coupled to the acquisition of an anti-viral status, which is dependent on the type I IFN signaling pathway.
The Summerlin Phenomenon
Authors: KULWANT S. Bhangoo
Journal: JAMA (1974)

<h3>To the Editor.—</h3> A paper on the application of solid medium method in allogenic transplantation, by A.H. Sidiqui and colleagues of the University of Amsterdam, was presented at the International Symposium on Wound Healing in Rotterdam, the Netherlands, in April 1974 and appears to be of relevance to the Sloan-Kettering affair (229:1391, 1974). These authors supported the thesis that allogenic skin undergoes antigenic attenuation during culture in vitro. Because of their impression that the conventional liquid culture medium leads to deterioration of the physical quality of the graft, they devised a solid (agar) culture medium and showed that while normal allogenic mouse skin, when grafted onto previously sensitized mice, was promptly rejected, allografts that had been first cultured for six weeks in the new solid medium were accepted when similarly transplanted to the sensitized mice. This phenomenon was limited to allografts and was not true of xenografts of similarly treated
Treatment of Classic Hemophilia: The Use of Fibrinogen Rich in Factor VIII for Hemorrhage and for Surgery
Authors: Campbell W. McMillan, Louis K. Diamond, Douglas M. Surgenor
Journal: New England Journal of Medicine (1961)

Effects of Fraction I in Surgical Intervention (Cases 8–15)As applied to the supportive management of patients with classic hemophilia undergoing various emergency and elective surgical procedures, fraction I therapy was associated with a spectrum of effects. Fraction I therapy instituted before and adequately maintained after operation. In 2 cases of appendectomy (Cases 8 and 9) and 2 of dental extractions (Cases 10a and 11), the exclusive use of fraction I for replacement therapy supported uneventful operative and postoperative phases. These surgical procedures progressed within clearly normal limits with 1 exception (Case 11), in which elective extraction of an abscessed . . .
Vitamin C and the common cold.
Authors: C W Wilson
Journal: BMJ (1971)

in which Dr. Linus Pauling's book Vitamin C and the Common Cold' was discussed.During the past six years a programme of research has been carried out in this department on various aspects of the metabolism and action of vitamin C, and several papers have now been published describing the results.27Included in this programme has been a study on the relationship between the administration of supplementary vitamin C and the occurrence of symptoms of the -common cold.Dr. Pauling referred to the results of these investigations in his book.Any discussion about vitamin C and the common cold must take into account the human requirements for exogenous vitamin C. The United Kingdom Panel on Recommended Allowances of Nutrients points out that there are two theories about the human
The Effect of Digoxin in the Splanchnic Circulation in Ventricular Failure
Authors: M. IRENÉ FERRER, STANLEY E. BRADLEY, HENRY O. WHEELER, YALE ENSON, RUDOLPH PREISIG, RÉJANE M. HARVEY
Journal: Circulation (1965)

Splanchnic hemodynamics were examined in 22 patients with heart disease, 16 of whom had evidence of ventricular insufficiency at the time of study. The response of the splanchnic vasculature to the exhibition of intravenous digoxin was also studied in nine of these subjects. Ventricular insufficiency was associated with splanchnic vasoconstriction proportional to a generalized increase in peripheral vascular resistance. Splanchnic blood volume was disproportionately increased with respect to total blood volume in patients having visceral congestion with right ventricular failure and combined ventricular failure. A significant relationship between central venous pressure and splanchnic blood volume was demonstrated in these cases. The greater elevation of the former than of the latter suggested the presence of splanchnic venoconstriction. The vascular readjustment to digoxin resulted in a relative intensification of the already existing vasoconstriction of the splanchnic bed as compared to the diffuse systemic vasodilatation which occurred at the same time as the consequence of the inotropic action of the drug: estimated splanchnic blood flow and splanchnic blood volume diminished at a time when systemic flow rose and peripheral vascular resistance decreased. The ultimate distribution of the volume of blood translocated out of the splanchnic bed during this process remains to be determined.
Place of delivery and adverse outcomes
Authors: D. Tuffnell
Journal: BMJ (2010)

Risks can be mitigated by early diagnosis and referral, but no birth is without risk

Planned birth at home or in a midwifery unit is part of the choice that should now be offered to women at low risk of complications. A recent large meta-analysis of mostly cohort studies (500 000 births) showed a doubling of the risk of excess neonatal deaths for home birth from 0.09% to 0.2%—one extra death in 900 births.1 However, the risks associated with birth in different settings are still uncertain because of the confounding factors inherent in observational data. These include differences in baseline risk, the intended or actual place of birth, demographics, parity, and standards of care. One randomised trial was piloted, but it looked at only 11 women⇓.2



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In the linked prospective cohort study (doi:10.1136/bmj.c5639), Evers and colleagues compared incidence rates of perinatal mortality and severe perinatal morbidity in the infants of low risk women who started labour in primary care (under a midwife) and high risk women who were under …
CARDIAC TROPONIN I AND B-TYPE NATRIURETIC PEPTIDE PREDICT CLINICAL OUTCOMES IN STABLE RENAL TRANSPLANT RECIPIENTS
Authors: Petr Jarolim, Brian Claggett, Marc Pfeffer, Anastasia Ivanova, Myra A. Carpenter, Andrew Bostom, John Kusek, Lawrence G. Hunsicker, Lisa Gravens-Mueller, Paul F. Jacques, Peter Finn, Scott Solomon, Andrew S. Levey
Journal: Journal of the American College of Cardiology (2014)