tbuckley/cabot-search huggingface dataset:
DVC1-0101 to Treat Peripheral Arterial Disease: A Phase I/IIa Open-label Dose-escalation Clinical Trial
Authors: Yoshikazu Yonemitsu, Takuya Matsumoto, Hiroyuki Itoh, Jin Okazaki, Makiko Uchiyama, Kumi Yoshida, Mitsuho Onimaru, Toshihiro Onohara, Hiroyuki Inoguchi, Ryoichi Kyuragi, Mototsugu Shimokawa, Hiroshi Ban, Michiko Tanaka, Makoto Inoue, Tsugumine Shu, Mamoru Hasegawa, Yoichi Nakanishi, Yoshihiko Maehara
Journal: Molecular Therapy (2013)

We here report the results of a Phase I/IIa open-label four dose-escalation clinical study assessing the safety, tolerability, and possible therapeutic efficacy of a single intramuscular administration of DVC1-0101, a new gene transfer vector based on a nontransmissible recombinant Sendai virus (rSeV) expressing the human fibroblast growth factor-2 (FGF-2) gene (rSeV/dF-hFGF2), in patients with peripheral arterial disease (PAD). Gene transfer was done in 12 limbs of 12 patients with rest pain, and three of them had ischemic ulcer(s). No cardiovascular or other serious adverse events (SAEs) caused by gene transfer were detected in the patients over a 6-month follow-up. No infectious viral particles, as assessed by hemagglutination activity, were detected in any patient during the study. No representative elevation of proinflammatory cytokines or plasma FGF-2 was seen. Significant and continuous improvements in Rutherford category, absolute claudication distance (ACD), and rest pain were observed (P < 0.05 to 0.01). To the best of our knowledge, this is the first clinical trial of the use of a gene transfer vector based on rSeV. The single intramuscular administration of DVC1-0101 to PAD patients was safe and well tolerated, and resulted in significant improvements of limb function. Larger pivotal studies are warranted as a next step. We here report the results of a Phase I/IIa open-label four dose-escalation clinical study assessing the safety, tolerability, and possible therapeutic efficacy of a single intramuscular administration of DVC1-0101, a new gene transfer vector based on a nontransmissible recombinant Sendai virus (rSeV) expressing the human fibroblast growth factor-2 (FGF-2) gene (rSeV/dF-hFGF2), in patients with peripheral arterial disease (PAD). Gene transfer was done in 12 limbs of 12 patients with rest pain, and three of them had ischemic ulcer(s). No cardiovascular or other serious adverse events (SAEs) caused by gene transfer were detected in the patients over a 6-month follow-up. No infectious viral particles, as assessed by hemagglutination activity, were detected in any patient during the study. No representative elevation of proinflammatory cytokines or plasma FGF-2 was seen. Significant and continuous improvements in Rutherford category, absolute claudication distance (ACD), and rest pain were observed (P < 0.05 to 0.01). To the best of our knowledge, this is the first clinical trial of the use of a gene transfer vector based on rSeV. The single intramuscular administration of DVC1-0101 to PAD patients was safe and well tolerated, and resulted in significant improvements of limb function. Larger pivotal studies are warranted as a next step.
The Non‐Specific Enhancement of Allergy I.
Authors: R. Pauwels, M. Van Der Straeten, B. Platteau, H. Bazin
Journal: Allergy (1983)

Bordetella pertussis organisms, with or without a small dose of alumhydroxide, enhance in rats the production of IgE antibodies to an unrelated antigen, even if this antigen has been administered 6 weeks beforehand. This non‐specific enhancement of IgE antibodies is accompanied by a substantial rise in total serum IgE and by the production of IgE antibodies to B. pertussis. The effect of B. pertussis on IgE synthesis is dose‐dependent. No effect of B. pertussis on IgE production can be observed in nude rats.
Desert Shield Makes History
Authors: Phil Gunby
Journal: JAMA (1991)

AS DIPLOMATS have sought to defuse the Iraq-Kuwait crisis, military medicine has deployed more sophisticated resources a greater distance more rapidly than ever in history for the Desert Shield operation. In case of war, military physicians would rely on aeromedical evacuation, such as is done with the Air Force's C-9<i>Nightingale</i>(top); on the hospital ships<i>Mercy</i>and<i>Comfort</i>, shown steaming together in the Persian Gulf (center); and on helicopter removal of wounded soldiers or marines from the battle zone, as is under way in this training exercise (bottom) (Air Force, Army, Navy photos)
Improving the Reliability of the Rebreathing Method for Measuring Mixed Venous Pco2
Authors: S. Godfrey
Journal: BMJ (1965)

the more lasting effects of pain relief is suggested, even though all sizes of fibres sustain some damage. Summary and ConclusionsThe neurotoxicity of ethoglucid given by arterial perfusion has been investigated in dogs in order to study the histological basis of the various effects noted in clinical practice.A direct toxic effect on nerve fibres of all types was found, and, in addition, damage to muscle and skin in the infused area was observed.A greater proportion of these effects appears to be reversible.The results support the hypothesis that relief of pain is primarily the result of damage to pain-nerve fibres, which occurs rapidly after administration of the drug, but they offer no definite explanation why this relief tends to persist while other neurological effects subside, although a theoretical possibility is discussed.The value of ethoglucid in the treatment of advanced malignant disease depends on its pain-relieving effect as well as its cytotoxic properties.Our thanks are due to Mr. F. D. Naylor for his assistance with the experiments and to Mr. K. Horton for preparing the histological sections.The ethoglucid used in this study was supplied by I.C.I.
Chickenpox in pregnancy. Pneumonitis more severe.
Authors: D Nathwani
Journal: BMJ (1993)

Recently we treated a 42 year old man with bowel obstruction at multiple sites due to advanced colonic carcinoma.A course of high dose steroids given eight months previously for radiotherapy induced emesis had resulted in a rapid evolution of a hypomanic state with complete insomnia.While treating him with steroids for his obstruction4 we infused 12mg of dexamethasone during the day and substituted a low dose of midazolam infusion at night.On this regimen his insomnia or hypomania did not recur and his bowel obstruction resolved on day 12.When he was converted to oral medication, diazepam 10mg was substituted for midazolam at night and he continued to sleep well.Sleep disturbance is not one of the best known side effects of steroids, but insomnia has medical and social sequelae that require recognition and action.Appropriate prescribing even in the most difficult cases may allow the patient enormous benefit from steroids and a good night's sleep.
Characteristics of t(8;21) acute myeloid leukemia (AML) with additional chromosomal abnormality: concomitant trisomy 4 may constitute a distinctive subtype of t(8;21) AML
Authors: K Nishii, E Usui, N Katayama, F Lorenzo V, K Nakase, T Kobayashi, H Miwa, M Mizutani, I Tanaka, K Nasu, H Dohy, T Kyo, M Taniwaki, T Ueda, K Kita, H Shiku
Journal: Leukemia (2003)
A Modified Ant Colony Optimization Algorithm for Tumor Marker Gene Selection
Authors: Hualong Yu, Guochang Gu, Haibo Liu, Jing Shen, Jing Zhao
Journal: Genomics Proteomics & Bioinformatics (2009)

Abstract Microarray data are often extremely asymmetric in dimensionality, such as thousands or even tens of thousands of genes but only a few hundreds of samples or less. Such extreme asymmetry between the dimensionality of genes and samples can lead to inaccurate diagnosis of disease in clinic. Therefore, it has been shown that selecting a small set of marker genes can lead to improved classification accuracy. In this paper, a simple modified ant colony optimization (ACO) algorithm is proposed to select tumor-related marker genes, and support vector machine (SVM) is used as classifier to evaluate the performance of the extracted gene subset. Experimental results on several benchmark tumor microarray datasets showed that the proposed approach produces better recognition with fewer marker genes than many other methods. It has been demonstrated that the modified ACO is a useful tool for selecting marker genes and mining high dimension data.
The inactive form of matrix metalloproteinase-9 is stored by liver collagens via the collagenous motive (GLY-PRO-HYP) X
Authors: Martin Ruehl, Rajan Somasundaram, Richard Farndale, Graham Knight, Monika Schmid, Renate Ackermann, Martin Zeitz, Detlef Schuppan
Journal: Journal of Hepatology (2002)
Air Pollution and Neonatal Blood Pressure: Examining Earlier Exposures
Authors: Wendee Nicole
Journal: Environmental Health Perspectives (2015)

Ambient air pollution has been associated in some studies (but not all) with increased blood pressure in adults 1 and children. 2,3A study in this issue of EHP examines even earlier exposures during gestation, an important period of ca rdiova scula r grow th a nd development. 4The results show a small but significant increase in newborn systolic blood pressure associated with exposure in the third trimester to black carbon (BC) and, to a lesser extent, fine particulate matter (PM 2.5 ).Researchers from Harvard Med ical School and the Harv ard T.H. Chan School of Public Health used data from 1,131 mother-infant pairs enrolled in Project Viva, a Boston based cohort study designed to investigate how diet and environ mental factors may affect maternal and newborn health. 5The study considered potential effects of sev eral air pollutants, including PM 2.5 , BC (a trafficrelated component of particulate pollution), nitrogen oxides, nitrogen dioxide, ozone, and carbon mon oxide.The authors used stationary monitoring data to estimate mothers' average air pollutant expo sures for each trimester and for the 90day period immediately preceding birth.On the day of birth, newborn systolic blood pres sure was measured up to five times, 1 minute apart.Mixedeffect models were adjusted for maternal age, maternal systolic blood pressure during the third trimester, newborn age (in hours), and newborn birth weight, all factors that had predicted newborn blood pressure in an earlier study. 5Models were also adjusted for sociodemographic variables and time trend."The most striking and significant findings are the third trimester associations between pollutants and newborn blood pres sure," says lead author Lenie van Rossem, an assistant professor at University Medical Center Utrecht in the Netherlands.Specifically, the researchers found that increased estimated exposures to outdoor PM 2.5 and BC in the third trimester-but not in the first and second trimesters-were associated with higher newborn systolic blood pressure.Interestingly, increased ozone exposure in the third trimester was associated with lower systolic blood pressure in newborns, whereas exposure in the second trimester was associated with higher blood pressure.Increased estimated exposures to carbon monoxide or nitrogen oxides during the second trimester also were associated with lower newborn systolic blood pressure. 4One possible explanation for these results is that gaseous pollutants such as ozone, nitrogen oxides, and carbon monoxide may affect blood pressure through a different biological pathway than particulate pollutants.
Revolutionary Medical Journalism
Authors: Sidney Benson
Journal: JAMA (1962)

<h3>To the Editor:—</h3> In spite of the prevalent feeling that there are too many journals published too frequently which contain, largely, duplications of material published elsewhere, a new journal will be published, the need for which has become increasingly apparent. <i>The Journal of Negative Results</i>will contain: (1) original articles presenting points of view which usually are not stated but need to be stated, (2) reports of results not obtained, and (3) commentary on material which has been published elsewhere, but which shouldn't have been. The editors of the<i>Journal</i>welcome such contributions if: (a) the author is willing to have the article appear anonymously (to allow freedom of expression and to avoid publication simply for the purpose of increasing the author's list), (b) the material submitted has not been published else-where by the author (lists of publications of the author shall accompany material submitted), (c) conclusions of the author
Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation
Authors: Kenyatta Cosby, Kristine S Partovi, Jack H Crawford, Rakesh P Patel, Christopher D Reiter, Sabrina Martyr, Benjamin K Yang, Myron A Waclawiw, Gloria Zalos, Xiuli Xu, Kris T Huang, Howard Shields, Daniel B Kim-Shapiro, Alan N Schechter, Richard O Cannon, Mark T Gladwin
Journal: Nature Medicine (2003)
IN FUTURE BATTLES WHERE SHALL THE FIELD HOSPITALS BE PLACED?
Authors: EDMUND ANDREWS
Journal: JAMA (1896)

Behind every fighting line there is a danger space within which lie the wounded. The modern long range rifles, and the new far reaching artillery have greatly widened this zone, while the increased rapidity of fire may sweep the ground with such fierceness that within its range ambulances can not approach, litter bearers can not carry off the wounded, and surgeons can not work. In case the field is very level and devoid of shelter, the problem of where to place the field hospitals, and how to get the wounded back to them has become one which greatly perplexes military surgeons. Take for instance the level plain on which Chicago stands. From Lake Michigan west to DesPlaines River, and from Evanston southward to Thornton extends a level plateau ten miles wide and thirty miles long, on which the natural contour of the ground affords not the slightest shelter from fire.
PARAPHIMOSIS OF THE CLITORIS
Authors: R. J. Willan
Journal: BMJ (1928)

SPLENOMEGALIC POLYCYTHAEMIA WITH HIGH BLOOD PRESSURE..I .ETM,"CAUIRA& thickened.The right kidney weighed 127 grams (4-1-ouncc and microscopically the larger arteries (interlobnlar, etc. showed considerable thickening of both middle and inncr coats, whilst the elomeruli showed hyaline swelling of their capillaries.Th re were decided deaefierative and necrotic changes in the epithelium of the con- voluted tubules, which were, however, doubtless ' terminal " in nature, or rather, of paulo-anite-
Reactions Following Intralesional and Sublesional Injections of Corticosteroids
Authors: Leon Goldman
Journal: JAMA (1962)

Intralesional and sublesional injections of relatively insoluble corticosteroids are still necessary for localized chronic dermatologic lesions where prolonged oral corticosteroid therapy is not desirable and where topical corticosteroid therapy, even the occlusive dressings or so-called surface depot therapy, is not effective. Reactions following intralesional and sublesional injections of corticosteroids are uncommon in relation to the large number of injections which are given. These uncommon reactions may be either local or even rarer, systemic types. Local reactions may include among others, transient atrophy, secondary infections and hypersensitivity reactions. Suggestions are offered to reduce the frequency of these reactions although it is recognized that they may occur in spite of all precautions and care.
Auditory processing disorders
Authors: D.-E. Bamiou, L. M Luxon
Journal: BMJ (2008)

Can cause educational, behavioural, and social problems but are often undiagnosed

Hearing impairment is the most common sensory disability worldwide and has a profound effect upon an individual’s ability to function at a personal, social, and occupation level. In February 2008, the Royal College of Physicians published a report about the diagnosis and management of hearing and balance disorders.1

The hearing process is underpinned by the transmission and analysis of sounds from the external ear to the auditory cortex. Disorders of the external, middle, and inner ear are well recognised, but recent advances have made us aware of hearing disorders related to the auditory nerve and brain.

In 1954 it was shown that brain pathology can lead to hearing difficulties that are not identified by conventional audiometry.2 More recent work has shown that hearing difficulties can be caused by disordered auditory processing within the brain across all age ranges. Auditory processing disorders result from impaired neural function and are characterised by poor recognition, discrimination, separation, grouping, localisation, or ordering of non-speech sounds.3 They may be developmental or acquired. The exact prevalence of auditory processing disorders is unknown, but they are estimated to affect around 5% of school aged children and an …
Comparative study of cutaneous leishmaniasis in human immunodeficiency virus (HIV)-infected patients and non-HIV-infected patients in French Guiana
Authors: P. Couppie, E. Clyti, M. Sobesky, F. Bissuel, P. Del Giudice, D. Sainte-Marie, J.P. Dedet, B. Carme, R. Pradinaud
Journal: British Journal of Dermatology (2004)

Few data are available on cutaneous leishmaniasis caused by dermotropic species in human immunodeficiency virus (HIV)-infected patients.To describe nine cases of cutaneous leishmaniasis in HIV+ patients and to compare their clinical features and their response to treatment with those of HIV- patients with the forms of leishmaniasis commonly found in French Guiana.A case-control study was carried out between July 1994 and December 2000 in French Guiana. We compared the following variables in nine HIV-infected patients with leishmaniasis and 27 matched controls: clinical type of leishmaniasis, number of lesions, presence of lymphangitis and adenopathy, the rate of recovery after treatment, and recurrence or reinfection.Eight of the HIV-infected patients had localized cutaneous leishmaniasis and one had mucocutaneous leishmaniasis. All of the controls had localized cutaneous leishmaniasis. Leishmania guyanensis was the only species isolated from HIV-infected subjects. HIV-Leishmania coinfected patients had a higher rate of recurrence or reinfection (P < 0.02) and a lower rate of recovery after one treatment cycle with pentamidine (P < 0.02) than did HIV- subjects. The CD4+ lymphocyte counts exceeded 200 mm(-3) in all HIV+ patients at the time of the diagnosis with leishmaniasis.In French Guiana, cutaneous leishmaniasis in moderately immunosuppressed HIV-infected subjects (> 200 CD4+ T cells mm(-3)) is characterized by a higher rate of recurrence or reinfection and is more difficult to treat than that in HIV- subjects.
Electrical and contractile activities of the human rectosigmoid.
Authors: S Sarna, P Latimer, D Campbell, W E Waterfall
Journal: Gut (1982)

Electrical and mechanical activities were recorded from the rectosigmoid of normal subjects using an intraluminal recording tube with two sets of bipolar electrodes and strain gauges. Four distinct types of electrical activities were recorded. (1) Electrical control activity (ECA). This activity varied in amplitude and frequency over time and the control waves were not phase-locked. The means of dominant frequency components in the lower and higher frequency ranges were 3.86 +/- 0.18 SD and 10.41 +/- 0.46 SD c/min, respectively. The overall dominant frequency component was mostly in the lower frequency range of 2.0-9.0 c/min. (2) Discrete electrical response activity (DERA). This activity appeared as short duration bursts (less than 10 s) of response potentials whose repetition rate was in the total colonic electrical control activity frequency range of 2.0-13.0 c/min. The mean duration of this activity was 2.24 +/- 1.30 SD s. (3) Continuous electrical response activity (CERA). This activity appeared as long duration bursts (greater than 10 s) of response potentials which were not related to electrical control activity. Its mean duration was 14.78 +/- 3.68 SD s. This activity generally did not propagate. (4) Contractile electrical complex (CEC). This activity appeared as oscillations in the frequency range of 25-40 c/min and was also not related to electrical control activity. This activity propagated, sometimes proximally and sometimes distally. Its mean duration was 18.87 +/- 9.22 SD s. The latter three types of electrical activities were all associated with different types of contractions. These contractions, however, did not always occlude the lumen. Colonic electrical control activity controls the appearance of discrete electrical response activity in time and space. The mechanism of generation of continuous electrical response activity and contractile electrical complex is not yet known.
Plague and the Peripheral Smear
Authors: Jonathan M. Mann
Journal: JAMA (1984)

The peripheral blood smear shown here was obtained from a fatal case of plague in a New Mexico resident. Plague was confirmed by isolation of<i>Yersinia pestis</i>from postmortem blood cultures. Plague is a zoonosis caused by the gram-negative coccobacillus<i>Y pestis</i>.<sup>1-4</sup>The disease is transmitted to humans either by flea vectors or, less commonly, by direct contact with plagueinfected animals, which can include dogs, cats, and other carnivores, in addition to the usual rodent and rabbit hosts of the disease. In addition, if a pneumonia secondary to hematogenous spread of<i>Y pestis</i>develops in patients with plague, person-to-person transmission of the disease becomes possible, thereby creating an urgent public health concern. After the introduction of rat plague to West Coast port cities in the late 19th and early 20th centuries, animal plague entered sylvatic rodent populations throughout the American West.<sup>2</sup>The first human plague reported in the
Mechanism of action of EGFR mutations
Authors: Raja Reddy
Journal: Thorax (2012)

Mechanism of action of EGFR mutationsThe role of mutant epidermal growth factor receptor (EGFR) kinases in the growth of a host of human cancers including lung cancer is well known.The activation of wild type EGFR is primarily driven by the binding of growth factors leading to receptor dimerisation.In this paper the authors, through a series of simulation experiments, show that the wildtype EGFR kinase domain is intrinsically disordered and it becomes ordered (active) only upon dimerisation.This intrinsic disorder ( partial unfolding) is a third functionally important conformation in addition to the previously identified 'αC-out inactive' and 'αC-in active' conformations.EGFR signalling involves multiple layers of controlling mechanisms; the identification of an intrinsically disordered state of EGFR kinase introduces another element critical for its function.EGFR mutations were generally assumed to give rise to spontaneous kinase activation, eliminating the dependence of the cancer mutants on dimerisation for activation.However the authors have been able to show that higher kinase activity of EGFR mutants like L834R mutation is due to a decreased threshold for dimerisation mediated activation (by suppression of the local intrinsic disorder) rather than to enhanced intrinsic catalytic potency of the mutant.The authors also found that phosphorylation of EGFR kinase domain at TYR 845 may suppress the intrinsic disorder and promote its dimerisation.This could potentially be a molecular mechanism for autonomous EGFR signalling.