tbuckley/cabot-search huggingface dataset:
Factors determining delayed peak flow in canine myocardial reactive hyperaemia
Authors: R. F. BELLAMY, H. S. LOWENSOHN, R. A. OLSSON
Journal: Cardiovascular Research (1979)

It has been suggested that delayed restoration of flow to the deeper layers of the myocardium is responsible for the gradual rise to peak flow rate characteristic of myocardial hyperaemia (RH). The distribution of coronary flow during RH was studied by injecting radiomicrospheres into the left atrium open chest dog preparations just prior to the end of a 15 s occlusion of the left circumflex branch. The artery was then reoccluded after 1, 2, or 4 s of RH. Myocardium perfused by the left anterior decending branch served as a control; the ratio of endocardial to epicardial (end/epi) perfusion in this bed averaged 1.14. During coronary occlusion and during the first second of RH the end/epi ratio in the hyperaemic zone averaged 50% of control, but rose progressively to equal control at the time of peak flow. Although evanescent subendocardial ischaemia may contribute to the gradual rise to peak flow rate it cannot by itself account for the time course of this response.
The Medical Profession in Mid-Victorian London
Authors: Lester S. King
Journal: JAMA (1978)

Although according to the jacket the author "traces the changing character of medical careers in the period from 1858 to 1886," the book actually ranges freely and widely over medical sociology of the whole 19th century and deals with subgroups of the medical profession, particularly the "medical elite" and the general practitioners. The author contrasts these groups in regard to education, professional opportunity, financial rewards, social status, and other sociological variables. The book seems to focus on the conflict between on the one hand the "elite" and on the other, the medical rank and file or other professional classes (such as nurses), lay groups (such as boards of hospital governors), or wider classes (such as "gentry")—all with special relevance to social and economic status. While the book offers a rather discursive account of various educational, social, and economic factors affecting different groups of medical practitioners, it ignores the vast overall
Kappa and delta opioid receptor stimulation affects cardiac myocyte function and Ca2+ release from an intracellular pool in myocytes and neurons.
Authors: C Ventura, H Spurgeon, E G Lakatta, C Guarnieri, M C Capogrossi
Journal: Circulation Research (1992)

We investigated the effects of mu, delta, and kappa opioid receptor stimulation on the contractile properties and cytosolic Ca2+ (Cai) of adult rat left ventricular myocytes. Cells were field-stimulated at 1 Hz in 1.5 mM bathing Ca2+ at 23 degrees C. The mu-agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (10(-5) M) had no effect on the twitch. The delta-agonists methionine enkephalin and leucine enkephalin (10(-10) to 10(-6) M) and the kappa-agonist (trans-(dl)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclo-hexyl]- benzeneacetamide)methanesulfonate hydrate (U-50,488H; 10(-7) to 2 x 10(-5) M) had a concentration-dependent negative inotropic action. The sustained decrease in twitch amplitude due to U-50,488H was preceded by a transient increase in contraction. The effects of delta- and kappa-receptor stimulation were antagonized by naloxone and (-)-N-(3-furyl-methyl)-alpha-normetazocine methanesulfonate, respectively. In myocytes loaded with the Ca2+ probe indo-1, the effects of leucine enkephalin (10(-8) M) and U-50,488H (10(-5) M) on the twitch were associated with similar directional changes in the Cai transient. Myofilament responsiveness to Ca2+ was assessed by the relation between twitch amplitude and systolic indo-1 transient. Leucine enkephalin (10(-8) M) had no effect, whereas U-50,488H (10(-5) M) increased myofilament responsiveness to Ca2+. We subsequently tested the hypothesis that delta and kappa opioid receptor stimulation may cause sarcoplasmic reticulum Ca2+ depletion. The sarcoplasmic reticulum Ca2+ content in myocytes and in a caffeine-sensitive intracellular Ca2+ store in neurons was probed in the absence of electrical stimulation via the rapid addition of a high concentration of caffeine from a patch pipette above the cell. U-50,488H and leucine enkephalin slowly increased Cai or caused Cai oscillations and eventually abolished the caffeine-triggered Cai transient. These effects occurred in both myocytes and neuroblastoma-2a cells. In cardiac myocyte suspensions U-50,488H and leucine enkephalin both caused a rapid and sustained increase in inositol 1,4,5-trisphosphate. Thus, delta and kappa but not mu opioids have a negative inotropic action due to a decreased Cai transient. The decreased twitch amplitude due to kappa-receptor stimulation is preceded by a transient increase in contractility, and it occurs despite an enhanced myofilament responsiveness to Ca2+. The effects of delta and kappa opioids appear coupled to phosphatidylinositol turnover and, at least in part, may be due to sarcoplasmic reticulum Ca2+ depletion.(ABSTRACT TRUNCATED AT 400 WORDS)
Weight in infancy and prevalence of coronary heart disease in adult life
Authors: C H D Fall, M Vijayakumar, D J P Barker, C Osmond, S Duggleby
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To determine whether low birth weight and low weight at 1 year are followed by an increased prevalence of coronary heart disease in adult life. <b>Design</b>: A follow up study of men born during 1920–30 whose birth weights and weights at 1 year were recorded. <b>Setting</b>: Hertfordshire, England. <b>Subjects</b>: 290 men born and still living in East Hertfordshire. <b>Main outcome measure</b>: The prevalence of coronary heart disease, defined by the Rose/WHO chest pain questionnaire, standard electrocardiographic criteria, or history of coronary artery angioplasty or graft surgery. <b>Results</b>: 42 (14%) men had coronary heart disease. Their mean birth weight, 7.9 lb (3600 g), was the same as that of the other men. Their mean weight at 1 year, 21.8 lb (9.9 kg), was 1 lb (454 g) lower (95% confidence interval 0.1 to 1.8, P=0.02). Percentages of men with coronary heart disease fell from 27% in those who weighed 18 lb (8.2 kg) or less at 1 year to 9% in those who weighed more than 26 lb (11.8 kg) (P value for trend=0.03). This trend occurred in both smokers and non-smokers and within each social class. <b>Conclusion</b>: These findings add to the evidence that coronary heart disease is "programmed" during early growth. <h3>Key messages</h3> Key messages This is consistent with the association between low weight at 1 year and increased death rates from coronary heart disease The association between low weight at 1 year and coronary heart disease occurs in smokers and non-smokers and in each social class This adds to evidence that influences acting before 1 year of age have an important effect on the risk of developing coronary heart disease
Home treatment for acute psychiatric illness.
Authors: C J Hawley
Journal: BMJ (1990)

several Gram positive bacteria but that other factors must also play a part, an observation consistent with our findings in Gram negative shock.6Nevertheless, if these results can be confirmed in vivo it will give added impetus to the trials of antibody to tumour necrosis factor as empirical treatment in septic shock.7We thank A Wienecke and Dr R Gilbert of the Food Hygiene Laboratory, CPHL Colindale, for toxin analysis of some of our strains.
Use and abuse of cotton buds
Authors: J. C Hobson
Journal: Journal of the Royal Society of Medicine (2005)

Ear injuries caused by cotton buds are commonly seen in ear, nose and throat (ENT) practice. We asked 1000 patients attending an ENT referral clinic whether they used cotton buds to clean the ear canal. Of the 325 who responded, 171 said they did. The frequency of use was no higher in those with ear complaints than in those with nose and other complaints. 15–20% of respondents disagreed with the statements that cotton buds can cause infections, wax impaction or perforations. On the evidence of this survey, manufacturers’ warnings need to be fortified.
INTERIM REPORT ON THE NEUROSYPHILIS INVESTIGATION OF THE MASSACHUSETTS COMMISSION ON MENTAL DISEASES
Authors: OSCAR J. RAEDER
Journal: American Journal of Psychiatry (1920)

1. In 428 cases of neurosyphilis treated during a period of four years, 129 cases or practically 30 per cent showed definite benefit. 125 cases are under treatment in hospitals of which a certain percentage can be expected to show similar improvement. Among 93 cases that have drifted away, another definite proportion, probably a larger number comparatively can be presumed to have benefited from treatment. 2. There are two definite groups of cases of neurosyphilis;the early or "psychopathic hospital" group and the advanced committable or "custodial group." The early case of the "psychopathic" type is not met with in insane hospitals—except in such as conduct out-patient departments. These cases also frequently first come to professional attention through the field of general or "internal" medicine. 3. The relatives (spouses, parents, offspring) of syphilitics and neurosyphilitics form a most important group in which not only syphilis but the earliest degrees of neurosyphilis, in the presymptomatic, often entirely unsuspected, stages, are brought to light by lumbar puncture and sero-analysis. It is in these types that by far the most benefit can be expected. 4. Early diagnosis preferable before pronounced mental symptoms have appeared gives the greatest promise of successful results. For it seems that for some reason, probably of a psysio-logico-chemical character, the curative agent is less able or practically unable to influence certain bacterial toxins after they have had time to combine with the neuroplasm. Another instance of this phenomenon is shown in the case of the tetanus toxin. 5. Apparently advanced neurosyphilis is not a contra-indication to treatment—there is a distinct, though not large—percentage of such cases that amply gratify the efforts of intensive attack. 6. In early and atypical cases the most exhaustive, and often, repeated, serological and spinal fluid examinations are the best guides to the diagnosis. The provocative method should not be overlooked. 7. Intensive and prolonged treatment to the point of saturation with the combined force of the three specifics, arsenic, mercury and potassium iodide. Arsphenamin has been preferred to neoarsphenamin as more lasting in its effects. 8. The therapia praesens of neurosyphilis is but a transition state in rational syphilotherapy. Medical science has discovered several good clues which must be followed up; and others ferreted out and run down before the solution of the problem is complete. Indeed the successful treatment of paresis and tabes as well as general vascular syphilis and visceral tertiaries such as the crippling cradio-pathia, etc., may ultimately be realized in the field of preventive medicine. With chemotherapy, however, Ehrlich has doubtless found the most vulnerable approach to the treponemiatic diseases, but further research is necessary and other combinations must be found before the life of this anthropophagous pest is successfully snuffed out.
Treatment of collagen-induced arthritis with lentiviral BiP improves clinical parameters of disease
Authors: A M Shields, P H Wooley, S J Thompson, L S Klavinskis, G S Panayi, M Antoniou, V M Corrigall
Journal: Annals of the Rheumatic Diseases (2010)

Rheumatoid arthritis (RA) is a chronic autoimmune disease manifesting primarily as an infl ammatory polyarthritis of the synovial joints.Gene therapy has the potential to permit the on August 19,
Optimal techniques for arterial gene transfer
Authors: L Feldman
Journal: Cardiovascular Research (1997)

Cardiovascular gene therapy is becoming a clinical reality due to improved vectors, delivery systems and careful experimental validation studies. Nearly all cardiovascular diseases are amenable to gene therapy, but the optimal combination of vector, delivery system and therapeutic gene is likely to be unique to each application. Currently, the most efficient vectors available are replication-defective adenoviral vectors, but transgene expression is limited in time due to a strong immune response. Conversely, non-viral vectors or plasmid DNA may be used safely but have very limited efficiency. Percutaneous, catheter-based delivery is feasible for most applications. The ultimate issues that will decide of the future of gene therapy are safety of the transfer and delivery techniques as well as cost/effectiveness comparisons with alternative therapies, including local delivery of drugs, proteins and/or mechanical devices.
Abstract 3295: Inhibiting vascular morphogenesis in tumors: EGFL7 as a novel therapeutic target
Authors: Stacey Yeung, Tanya Smyczek, Jason Cheng, Anthony Lima, Rafael Molina, Patricia Hamilton, Jason Long, Leanne Berry, Michelle Nannini, Kai Barck, Hani Bou-Reslan, Tim Cao, Calvin Ho, Richard Carano, Ian Kasman, Greg Plowman, Mallika Singh, Weilan Ye, Leisa Johnson
Journal: Cancer Research (2011)

Abstract EGFL7 is a vascular restricted extracellular matrix protein that is up-regulated during angiogenesis (Campagnolo et al., 2005; Fitch et al., 2004; Parker et al., 2004; Soncin et al., 2003). EGFL7 supports endothelial cell adhesion (Parker et al., 2004; Schmidt et al., 2007) and protects endothelial cells from stress-induced apoptosis (Xu et al., 2008). Inhibition of Egfl7 expression in zebrafish embryos abolished vascular lumen formation and reduced sprouting angiogenesis (Parker et al., 2004). We developed a panel of anti-EGFL7 monoclonal antibodies that block the adhesive and pro-survival activities of EGFL7. Anti-EGFL7 in combination with anti-VEGF resulted in significant tumor regression in multiple murine xenograft models, whereas anti-VEGF alone only slowed tumor growth in the same models. Anti-EGFL7 monoclonal antibodies also demonstrated prolonged survival and anti-tumor angiogenesis effects in stringent murine genetic tumor models when used as a single agent, and enhancement of anti-VEGF therapy in the combination setting. An ongoing Phase I study is being conducted to evaluate clinical safety, PK, PD and efficacy of anti-EGFL7. References: Campagnolo, L., Leahy, A., Chitnis, S., et al. EGFL7 is a chemoattractant for endothelial cells and is up-regulated in angiogenesis and arterial injury. Am J Pathol (2005) 167, 275-284. Fitch, M. J., Campagnolo, L., Kuhnert, F., et al. Egfl7, a novel epidermal growth factor-domain gene expressed in endothelial cells. Dev Dyn (2004) 230, 316-324. Parker, L. H., Schmidt, M., Jin, S. W., et al. The endothelial-cell-derived secreted factor Egfl7 regulates vascular tube formation. Nature (2004) 428, 754-758. Schmidt, M., Paes, K., De Maziere, et al. EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution. Development (2007) 134, 2913-2923. Soncin, F., Mattot, V., Lionneton, F., et al. VE-statin, an endothelial repressor of smooth muscle cell migration. Embo J (2003) 22, 5700-5711. Xu, D., Perez, R. E., Ekekezie, I., et al. Epidermal growth factor-like domain 7 protects endothelial cells from hyperoxiainduced cell death. Am J Physiol Lung Cell Mol Physiol (2008) 294, L17-L23. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3295. doi:10.1158/1538-7445.AM2011-3295
Serum Cholesterol in Wisconsin Epidemiologic Study of Diabetic Retinopathy
Authors: Barbara E K Klein, Scot E Moss, Ronald Klein, Tanya S Surawicz
Journal: Diabetes Care (1992)

Objective To describe serum total and high-density lipoprotein (HDL) cholesterol in a sample of people with diabetes. Research Design and Methods Subjects were those who participated in the 1984-1986 Wisconsin Epidemiologic Study of Diabetic Retinopathy. Data were from three groups of subjects: 304 younger-onset and 185 older-onset people taking insulin and 162 older-onset individuals not taking insulin. Serum lipids, duration of diabetes, glycosylated hemoglobin, diastolic blood pressure, sex, age, serum creatinine, units of insulin per kiliogram per day, smoking status, serum C-peptide level, and alcohol use were analyzed statistically. Results In subjects taking insulin, glycosylated hemoglobin was correlated most strongly with total cholesterol. In those not taking insulin, C-peptide was correlated most strongly. In subjects taking insulin, the units used per day (fewer)and sex (female) were significantly associated with higher HDL cholesterol, and in both older-onset groups, serum C-peptide was significantly associated with lower HDL cholesterol. Mean total cholesterol levels were generally higher and mean HDL cholesterol levels were generally lower than those found in a nondiabetic comparison group. Conclusions By the National Cholesterol Education Program guidelines, 17% of younger-onset and 30% of older-onset insulin users and 32% of olderonset subjects not taking insulin were in the high-risk range for total cholesterol. Lower levels of glycosylated hemoglobin might result in lower cholesterol levels.
Vascular Wall Progenitor Cells in Health and Disease
Authors: Peter J. Psaltis, Robert D. Simari
Journal: Circulation Research (2015)

The vasculature plays an indispensible role in organ development and maintenance of tissue homeostasis, such that disturbances to it impact greatly on developmental and postnatal health. Although cell turnover in healthy blood vessels is low, it increases considerably under pathological conditions. The principle sources for this phenomenon have long been considered to be the recruitment of cells from the peripheral circulation and the re-entry of mature cells in the vessel wall back into cell cycle. However, recent discoveries have also uncovered the presence of a range of multipotent and lineage-restricted progenitor cells in the mural layers of postnatal blood vessels, possessing high proliferative capacity and potential to generate endothelial, smooth muscle, hematopoietic or mesenchymal cell progeny. In particular, the tunica adventitia has emerged as a progenitor-rich compartment with niche-like characteristics that support and regulate vascular wall progenitor cells. Preliminary data indicate the involvement of some of these vascular wall progenitor cells in vascular disease states, adding weight to the notion that the adventitia is integral to vascular wall pathogenesis, and raising potential implications for clinical therapies. This review discusses the current body of evidence for the existence of vascular wall progenitor cell subpopulations from development to adulthood and addresses the gains made and significant challenges that lie ahead in trying to accurately delineate their identities, origins, regulatory pathways, and relevance to normal vascular structure and function, as well as disease.
Uptake of Adenoviral Vectors via Fibroblast Growth Factor Receptors Involves Intracellular Pathways That Differ from the Targeting Ligand
Authors: Diana K. Hoganson, Barbara A. Sosnowski, Glenn F. Pierce, John Doukas
Journal: Molecular Therapy (2001)

Target-specific delivery of adenoviral gene therapy vectors has been achieved by introducing basic fibroblast growth factor (FGF2) onto viral capsids. FGF2-retargeted vectors enter the cell through high-affinity FGF receptors while normal adenoviral receptor interactions are ablated. In addition, FGF2-mediated targeting permits a higher level of transgene expression and in vivo efficacy. We now present studies on the intracellular pathways and mechanisms of transduction by FGF2-retargeted adenovirus. FGF2 retargeting results in increased virion entry. Nuclear delivery is also increased, but to a level that is directly proportional to virion entry. In addition, after entry, the retargeted particle rapidly localizes to the nucleus in a time frame similar to that of adenovirus alone. Transgene expression is always enhanced with FGF2-mediated delivery, whether overall transduction of the population is increased, equivalent, or decreased relative to nontargeted adenoviral vectors. However, the increase in transgene expression does not correlate quantitatively with enhanced cellular entry, indicating that other factors may influence transgene expression levels. The increase in transgene expression occurs only when the FGF2-retargeting moiety is physically complexed with the adenoviral vector, indicating a requirement for a spatial link between the ligand and the virus particle. The FGF2–adenoviral complex activates the FGF receptor-mediated proliferative signaling cascade, but this signal transduction is not required for the enhanced level of gene expression observed after FGF2-mediated delivery. These findings emphasize that, in addition to altering receptor tropism, the influence of FGF2 retargeting extends to intracellular adenoviral trafficking pathways. Although the increased delivery of virions into the cell and nucleus contributes to the enhanced transgene expression observed with FGF2 retargeting, other as yet undefined cellular mechanisms also contribute to this process.
An arteriosclerotic chiasmal syndrome. Bitemporal hemianopia associated with fusiform dilatation of the anterior cerebral arteries
Authors: G. F. Hilton
Journal: JAMA (1966)

IN A REVIEW of the blood supply to the optic chiasm published in 1958, Hughes implied that arteriosclerosis in the elderly patient can, on rare occasions, cause  classical chiasmal syndrome (optic atrophy, bitemporal field -defects, and  normal sella turcica).1He referred specifically to the case of  74-year-old man with generalized arteriosclerosis who suffered the abrupt onset of uppertemporal-field defects, and he deduced from findings in this case and from findings in a few related cases that the responsible occlusive vascular changes had occurred in small prechiasmal vessels derived from the anterior cerebral arteries.  In 1960, Walsh and Gass called attention to  direct effect of sclerotic anterior cerebral arteries on the chiasm.2They showed  necropsy specimen (Fig 1) in which they found compression and distortion of the chiasm and optic nerves by sclerotic, elongated, and prolapsed anterior cerebral arteries. They had no information regarding
Physiological responses of wheelchair athletes at percentages of top speed.
Authors: I G Campbell, C Williams, H K Lakomy
Journal: British Journal of Sports Medicine (1997)

Wheelchair athletes often select a percentage of their top speed (%TS) to determine training intensity. The aim of the study was to determine whether choosing a %TS corresponds to the physiological concept of relative exercise intensity (% peak oxygen uptake: %VO2 peak) and to examine selected physiological and metabolic responses of a group of wheelchair athletes to 60 minutes' exercise at 80% TS.12 male wheelchair athletes (10 paraplegics and two tetraplegics) performed a series of tests on a motorised treadmill adapted for wheelchairs. The tests, which were undertaken on separate occasions, included the determination of VO2 peak, the determination of oxygen cost at a range of submaximal wheelchair propulsion speeds, and a 60 min exercise test at 80% TS.Wheelchair propulsion speeds equivalent to 60%, 70%, 80%, and 90% of each subject's TS were found to equate to 48.3 (SD13.8)%, 60.0(11.1)%, 70.6(9.8)%, and 82.7(9.6)% of VO2 peak, with a wide variation in the relative exercise intensities evident at each %TS. During the 1 h exercise test at 80% TS the physiological and metabolic responses measured were indicative of steady state exercise, with no signs of fatigue evident.The results of this study suggest that selecting a %TS is not an appropriate way of selecting a common relative exercise intensity. There may also be a need for the current training practises of some wheelchair road racers to be modified.