tbuckley/cabot-search huggingface dataset:
Senior house officer training: is it getting better? A questionnaire survey
Authors: E. Paice, G. West, R. Cooper, V. Orton, A. Scotland
Journal: BMJ (1997)

Objective: To investigate the role of a patent foramen ovale in the pathogenesis of multiple brain lesions acquired by sport divers in the absence of reported decompression symptoms.Design: Prospective double blind cohort study.Setting: Diving clubs around Heidelberg and departments of neuroradiology and neurology.Subjects: 87 sport divers with a minimum of 160 scuba dives (dives with self contained underwater breathing apparatus).Main outcome measures: Presence of multiple brain lesions visualised by cranial magnetic resonance imaging and presence and size of patent foramen ovale as documented by echocontrast transcranial Doppler ultrasonography.Results: 25 subjects were found to have a right-to-left shunt, 13 with a patent foramen ovale of high haemodynamic relevance.A total of 41 brain lesions were detected in 11 divers.There were seven brain lesions in seven divers without a right-to-left shunt and 34 lesions in four divers with a right-to-left shunt.Multiple brain lesions occurred exclusively in three divers with a large patent foramen ovale (P = 0.004).Conclusions: Multiple brain lesions in sport divers were associated with presence of a large patent foramen ovale.This association suggests paradoxical gas embolism as the pathological mechanism.A patent foramen ovale of high haemodynamic relevance seems to be an important risk factor for developing multiple brain lesions in sport divers.
The Association Between Local Diagnostic Testing Intensity and Invasive Cardiac Procedures
Authors: David E. Wennberg
Journal: JAMA (1996)

To determine the extent to which geographic variation in invasive cardiac procedures can be explained by the variable use of diagnostic testing.A population-based cohort study using Medicare Part B data (physician services).Procedure data for all Medicare beneficiaries in northern New England.Twelve coronary angiography service areas were constructed for Medicare beneficiaries in northern New England. Age- and sex-adjusted utilization rates were developed for three procedure categories: total stress test, coronary angiography, and revascularization. Total stress tests were further stratified into nonimaging and imaging procedures (eg, thallium). Tests performed in follow-up to invasive procedures were excluded (eg, stress test following revascularizations). Linear regression was used to assess the relationship between procedure categories.A tight positive relationship was found between total stress test rates and the rates of subsequent coronary angiography (R2=0.61, P<.005). Most of the variance was explained by imaging stress tests (R2=0.50, P<.02). A strong relationship was found between coronary angiography and revascularization (R2=0.82, P<.001). Finally, a clear relationship between total stress tests and subsequent revascularizations was also found (R2=0.55, P<.006).The population-based rates of diagnostic testing largely explained the variance associated with subsequent therapeutic interventions. Our results suggest that local testing intensity is an important determinant of the variable use of invasive cardiac procedures.
Dobutamine Stress Echocardiography
Authors: David S. Bach, Kim A. Eagle
Journal: Circulation (1997)

Poldermans et al have added important data to the body of literature supporting the use of dobutamine stress echocardiography to define long-term cardiac risk for patients undergoing major vascular surgery. In the application of this or any other noninvasive study, it will remain important to select the appropriate population for testing. In the case of noninvasive testing before vascular surgery, the population should consist of patients at intermediate risk of an adverse cardiac event rather than the whole population with known or suspected coronary artery disease. If this is done, testing can be restricted to a group for whom results will affect clinical decision making. Clinical assessment should remain the first method of patient screening. Among patients identified by clinical markers as at intermediate risk for a perioperative or late cardiac event, noninvasive testing such as dobutamine stress echocardiography may be used to better stratify risk and to help guide perioperative and subsequent cardiac management.
Pathogenic T cells have a paradoxical protective effect in murine autoimmune diabetes by boosting Tregs
Authors: Yenkel Grinberg-Bleyer, David Saadoun, Audrey Baeyens, Fabienne Billiard, Jérémie D. Goldstein, Sylvie Grégoire, Gaëlle H. Martin, Rima Elhage, Nicolas Derian, Wassila Carpentier, Gilles Marodon, David Klatzmann, Eliane Piaggio, Benoît L. Salomon
Journal: Journal of Clinical Investigation (2010)

CD4+CD25+Foxp3+ Tregs play a major role in prevention of autoimmune diseases. The suppressive effect of Tregs on effector T cells (Teffs), the cells that can mediate autoimmunity, has been extensively studied. However, the in vivo impact of Teff activation on Tregs during autoimmunity has not been explored. In this study, we have shown that CD4+ Teff activation strongly boosts the expansion and suppressive activity of Tregs. This helper function of CD4+ T cells, which we believe to be novel, was observed in the pancreas and draining lymph nodes in mouse recipients of islet-specific Teffs and Tregs. Its physiological impact was assessed in autoimmune diabetes. When islet-specific Teffs were transferred alone, they induced diabetes. Paradoxically, when the same Teffs were cotransferred with islet-specific Tregs, they induced disease protection by boosting Treg expansion and suppressive function. RNA microarray analyses suggested that TNF family members were involved in the Teff-mediated Treg boost. In vivo experiments showed that this Treg boost was partially dependent on TNF but not on IL-2. This feedback regulatory loop between Teffs and Tregs may be critical to preventing or limiting the development of autoimmune diseases.
Drugs agency grants its first licence to homoeopathic product
Authors: D. Cohen
Journal: BMJ (2009)

The United Kingdom’s drugs agency has given a licence to the makers of a homoeopathic product, despite scientists and researchers saying that no evidence shows that it works.

Since September 2006 the Medicines and Healthcare Products Regulatory Agency (MHRA) has been allowed to grant licences to traditional therapies if their use “is plausible on the basis of long standing use and experience” and no evidence shows that they cause harm.

At the end of last month, Nelsons Arnicare Arnica 30c pillules became the first product in the UK to be given such a licence by the agency, which will enable its manufacturers to make therapeutic claims for it.

Edzard Ernst, the UK’s only professor of complementary medicine, said that the agency’s national rules scheme was “making a mockery of evidence based medicine.”

On the packaging, the makers will be able to describe the product as “a homoeopathic medicinal product used within the homoeopathic tradition for the symptomatic relief of sprains, muscular aches, and bruising or swelling after contusions.”

Professor Ernst says that the remedy based on the plant Arnica montana has been subject to more controlled clinical trials than any other homoeopathic treatment.

“There is no good evidence for arnica,” he said. “It …
A CONVENIENT METHOD FOR CLEANSING THE MEATUS PRIOR TO CATHETERIZATION
Authors: James Raglan Miller
Journal: JAMA (1928)

The customary method of cleansing the urethral meatus before inserting the catheter calls for several ounces of antiseptic solution and pledgets of cotton in a finger bowl or other container. I have been using with great satisfaction Leonardo and Feirer's S. T.-37 (Sharp &amp; Dohme) in an ordinary deVilbiss atomizer. The following advantages are noted: 1. Convenience. The solution is instantly available and does not require special preparation. 2. Economy. A very small amount of solution is used. 3. Thorough cleansing. I have found that this method not only cleanses the surrounding parts but also spreads the meatus and literally washes out any discharge within 0.5 cm. of the meatus. This is done without trauma or discomfort to the patient. 4. Simplicity of technic. The labia can be held apart during the entire procedure, while the meatus is cleansed with the atomizer held in the right hand and while the catheter is inserted.
Identification of Channels Promoting Calcium Spikes and Waves in HT1080 Tumor Cells
Authors: Ji-Biao Huang, Andrei L. Kindzelskii, Andrea J. Clark, Howard R. Petty
Journal: Cancer Research (2004)

Abstract Intracellular Ca2+ signals have been associated with cell polarization and locomotion. As cell motility underlies metastasis, we have sought to better characterize the Ca2+ signaling events in HT1080 fibrosarcoma cells. We have tested the hypothesis that low voltage-activated (LVA) and nonvoltage-gated (NVG) channels of HT1080 cells participate in dynamic Ca2+-signaling events leading to cell migration and invasion. Immunofluorescence microscopy has shown that HT1080 cells express LVA T-type Ca2+ channels uniformly about the cell periphery, whereas the transient receptor potential-1 (a NVG cation channel) protein appears as punctate spots about a cell’s periphery. HT1080 cells exhibit periodic intracellular Ca2+ spikes. High-speed imaging revealed that the Ca2+ spikes were composed of a single Ca2+ wave traveling unidirectionally about the periphery of the cytoplasm in a clockwise fashion (as viewed from basal to apical surfaces). The T-type Ca2+ channel blocker mibefradil inhibited Ca2+ spikes and waves on cells and, in parallel, inhibited cell motility and invasion in a dose-dependent manner. Similar changes were noted with the NVG cation channel blockers Gd3+ and carboxyamido-triazole. The combination of LVA and NVG blockers further reduced Matrigel invasiveness. However, the Ca2+ channel blockers nicardipine, SKF96365, diltiazem, and verapamil had no effect at appropriate doses. These results indicate that certain LVA and NVG channels regulate HT1080 cell motility. In addition to providing novel information regarding cancer cell motility, we suggest that it may be possible to design drugs that inhibit a key Ca2+ wave, thereby enhancing the efficacy of emerging therapeutic protocols.
Genetic Targeting of Adenovirus Vectors Using a Reovirus σ1-Based Attachment Protein
Authors: Frederik H.E. Schagen, Felix M. Wensveen, Jan E. Carette, Terence S. Dermody, Winald R. Gerritsen, Victor W. van Beusechem
Journal: Molecular Therapy (2006)

Targeting adenovirus vectors (AdV's) for selective transduction of specific cell types requires ablation of native adenovirus tropism and introduction of a unique target-binding moiety. To bring these requirements within reach, we developed a novel strategy to target AdV's genetically that relies on replacement of the entire adenovirus fiber protein with a fusion molecule comprising the virion-anchoring domain of fiber and the oligomerization domain of reovirus attachment protein σ1. The chimeric molecule forms trimers, is transported to the nucleus, and assembles onto the adenovirus capsid. In contrast to previously reported genetically targeted vectors, the AdV presented herein propagates efficiently without a requirement for complementing fiber. Due to ablation of the native adenovirus tropism, the infectivity of this AdV was at least 35-fold reduced on 293 cells. Importantly, a His tag incorporated into the chimeric attachment protein conferred His-tag-dependent tropism to the AdV, which resulted in a 12- to 40-fold greater transduction efficiency on two different cell lines expressing a His-tag-binding receptor. In addition, the infection efficiency was strongly reduced by preincubation with a His-tag-specific Ab. Thus, this σ1-based chimeric attachment molecule provides a promising new platform for the generation of truly targeted AdV's.
Treatment of Primary Pulmonary Hypertension with Continuous Intravenous Prostacyclin (Epoprostenol)
Authors: Lewis J. Rubin
Journal: Annals of Internal Medicine (1990)

Study Objective: To determine the efficacy of continuous intravenous infusion of prostacyclin (epoprostenol) in primary pulmonary hypertension. Design: Randomized trial with 8-week treatment periods and nonrandomized treatment for up to 18 months. Setting: Four referral centers. Patients: Sequential sample of 24 patients with primary pulmonary hypertension. Nineteen patients completed the study. Four patients died and one left the study because of adverse effects (pulmonary edema). Interventions: Continuous intravenous prostacyclin administered by portable infusion pump at doses determined by acute responses during baseline catheterization in ten patients. Nine patients were treated with anticoagulants, oral vasodilators, and diuretics. Measurements and Main Results: Starting with a baseline value for total pulmonary resistance of 21.6 units, there was a decrease of 7.9 units (95% CI, -13.1 to -2.2; P = 0.022) in the prostacyclin-treated group after 8 weeks; there was virtually no change in the conventional therapy group (from 20.6 to 20.4 units, not significant). Six of ten prostacyclin-treated patients who completed the 8-week study period had reductions in mean pulmonary artery pressure of greater than 10 mm Hg, whereas only one of nine in the conventional treatment group had a similar response (P = 0.057). Nine patients receiving prostacyclin for up to 18 months have persistent hemodynamic effects, although dose requirements have increased with time. Complications have been attributable to the drug delivery system. Conclusions: Prostacyclin produces substantial and sustained hemodynamic and symptomatic responses in severe primary pulmonary hypertension and may be useful in the management of some patients with this disease.
Characterisation of personal Der p 1 exposure from upper bedding, when placed in a clean environment
Authors: J.Y. Lau, J.K. Sercombe, E.R. Tovey
Journal: Journal of Allergy and Clinical Immunology (2005)

RATIONALE: The aim of this study was to model the amount and sources of mite allergen Der p 1 attributable to bedding, when placed in an environment that was otherwise free of allergen. METHODS: Bedding (pillow, pillowcase, blanket, blanket cover and mattress sheet) from homes (n=19) was fitted to an allergen free mattress within an allergen free room. Der p1 exposure was assessed in triplicate by a person collecting intranasal air samples while lying in bed and by three sets of fixed IOM air samplers running at 2L/min 1 m above the bed, near the head and between the sheets. Reservoir samples were taken from bedding by vacuuming and tape rolling. Der p 1 was assayed by amplified ELISA. RESULTS: A median of 147 pg (range 40.4-1133.7) of Der p1 was inhaled in 20 minutes. Median Der p1 levels in ambient air and near the head were 6.07 and 6.66 pg/m3 respectively. The median quantity of Der p1 collected using an IOM sampler placed between the upper and lower bed sheets was 6.85 ng/m3 (range 1.15-22.36). The between sheet samples were the only samples that correlated with inhaled Der p 1 (r = 0.68, p=0.01). Interclass correlation for intranasal samples was 0.58 and for IOM samples was 0.24. CONCLUSIONS: Inhaled Der p 1 did not correlate with reservoir measurements, expressed as μg/area or μg/g from bedding or ambient air samples collected around the bed using fixed air samplers, but were correlated with samples collected by an air pump located between the bed sheets.
Garcia da Orta
Authors: L. Pelner
Journal: JAMA (1966)

Just three years ago, Portugal honored one of her most famous sons, Garcia da Orta, by issuing a series of postage stamps in his honor<sup>1</sup>(Fig 1). The occasion was 400 years after the publication of his remarkable work which catalogued, discussed, evaluated, and detailed the method of cultivation of many tropical plants that were then not known to Europeans. He first described Asiatic cholera and its manifestations and also performed the first autopsy on an Indian subject with this disease. He has been called the Father of Pharmacognosy.<sup>2</sup>He was one of the founders of the great city of Bombay, India. In Bombay, he had one of the most remarkable botanical gardens in the subcontinent, where he grew many exotic tropical medicinal plants and spices. However, in recent correspondence with the Indian Tourist Bureau regarding da Orta, nothing is mentioned about his connection with the founding of
NOTES ON CHRONIC HEART-DISEASE
Authors: A. Harvey
Journal: BMJ (1854)

Ix the following notes, an attempt is made to exhibit within as small a compass as possible, and in a form appraching the tabular, the leading facts connected with the pathology, diagnosis, and prognosis, of the more common organic affections of the heart.Imperfect as the notes are, the author is not without hope that they may be of service to some of his colleagues in the ASSocIATION, who, though familiar with the subject of heartdisease, may not always be able at once or readily to call to mind such par- ticulars respecting it as they must often have occa- sion for in the course of their practice, and which they may not always have time or opportunity to collect from luger treatises.It may be added, that the notes were originally drawn up for the students attending the author's class, and deli- vered to them as a recapitulation of the facts just previously detailed at greater length in the lectures; and that the materials of them are chiefly taken from Dr. Watson's Lecture.and Dr. Alison's Outlines of Pathotogy and Prac- Wce of .Aedicine, the works used in the class as text-books.I. DISEASE OF VALVES AND ORIFICES.i.The valves and orifices of the left side of the heart are at least twenty times more liable to disease than the valves and orifices of the right side.Disease of the semilunar pulmonary valves is so rare as to be matter of pathological interest merely.Disease of the tricuspid valves is more frequently, although still sel- dom, met with; and still seldomer without coexisting dis- ease of either the aortic or mitral valves.II.In early life and in women, the mitral valve and cor-
The Case for: Hypoglycemia Is of Cardiovascular Importance
Authors: Nebojsa M. Lalic
Journal: Diabetes Care (2013)

Hypoglycemia, defined as a plasma glucose concentration <70 mg/dL, represents a major and potentially very dangerous side effect of glucose-lowering therapies in patients with diabetes, and it challenges the patient’s ability to achieve and maintain optimal glycemic control (1–3). Statistically, the incidence of mild hypoglycemia in patients with type 1 diabetes is ~30 episodes/patient/year, whereas the incidence of severe hypoglycemia (i.e., requiring third-party assistance) may be as high as 3.2 episodes/patient/year (4). Furthermore, an estimated 2–4% of deaths of people with type 1 diabetes have been attributed to hypoglycemia. On the other hand, patients with type 2 diabetes experience hypoglycemia less frequently, with an incidence of mild and severe hypoglycemic episodes of 2–10/patient/year and 0.1–0.7/patient/year, respectively (4).

The occurrence of hypoglycemia, both in experimental and human settings even without diabetes or related metabolic changes, provokes substantial increase in counterregulatory hormonal secretion and affects the cardiovascular system and the brain, in turn affecting cognition, mood, and the level of consciousness. The secretion of counterregulatory hormones—of which glucagon and epinephrine are the most potent but also including norepinephrine, vasopressin, growth hormone, and cortisol—follows suppression of endogenous insulin secretion (5).

In addition, a specific response that occurs within the brain includes the activation of the central sympathetic nervous system, which promotes autonomic symptoms such as sweating, tremor, a pounding heart, hunger, and anxiety (6). Severe hypoglycemia is associated with significant morbidity such as cognitive impairment and can cause major neurological disability, including difficulty concentrating, drowsiness, and poor coordination. When blood glucose falls below 2.8 mmol/L, the majority of cognitive modalities are impaired. It is essential for a patient to be aware of these neuroglycopenic symptoms because they warn him/her that prompt action is required to treat the hypoglycemia and restore blood glucose to normal. In rare cases, prolonged severe …
THE TREATMENT OF PSYCHONEUROSES IN GENERAL PRACTICE
Authors: LAUREN H. SMITH
Journal: JAMA (1934)

The treatment of psychoneuroses in general practice should be viewed with a broad meaning. Besides the common psychoneuroses, I will include the use of psychotherapy in distressing physical diseases, or in cases of any sort in which there may be an emotional or mental problem, and with any individual who might consult us as physicians for advice on any personal problem involving mental and physical adjustment to life. Patients suffering from frank mental disease need definite psychotherapy and other medical therapy, but consideration of this phase of the field is not included here. In the classification of the psychoneuroses, one finds general agreement on four central types or symptom complexes; namely, neurasthenia, hysteria, psychasthenia and psychoneurotic anxiety states. The last group includes anxiety hysteria and anxiety neurosis. The latter conditions are difficult to differentiate definitely and for the purpose of this paper such differentiations are unimportant. <h3>ETIOLOGIC FACTORS</h3> The psychoneuroses
M36 Evaluating Aerosol Administration Of A Candidate Tb Vaccine Mva85a
Authors: Z. M. Thomas, I. Satti, S. Harris, J. Meyer, S. Sheehan, H. Bettinson, H. McShane
Journal: Thorax (2014)

<h3></h3> There is an urgent need for a better vaccine against TB than BCG, which confers variable protection against pulmonary TB, the main source of TB transmission. Heterologous prime-boost vaccination regimens using virally-vectored vaccines induce strong cellular immune responses and are a leading strategy for TB vaccine development. Boosting BCG with MVA85A, a recombinant viral vector expressing antigen 85A, can enhance BCG induced protection in animal models. MVA85A in humans is safe and immunogenic when administered systemically. Animal data suggests delivering a vaccine to the respiratory mucosa may be the most protective route. We recently completed the first trial where a virally-vectored vaccine, MVA85A, was delivered to humans by aerosol; and was found to be safe and highly immunogenic. This route also has potential for dose-sparing. A limitation of virally-vectored vaccines is anti-vector immunity, which limits use and re-use. Non-human primate data with aerosolised MVA85A suggests that aerosol vaccination induces less systemic anti-vector immunity than systemic routes. We have demonstrated this is also true in humans in our first aerosol trial, where humoral anti-vector immunity to MVA was induced by volunteers vaccinated by the systemic route but not the aerosol route. An on-going trial now addresses the question, if alternating routes of vaccination can abrogate anti-vector immunity, by immunising twice with MVA85A by heterologous routes one month apart. This would be an important development for the development of aerosolised TB vaccines but also for new vectored vaccines for RSV, universal influenza and a range of bacterial respiratory pathogens.
Atorvastatin and uptake of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) in human monocyte–macrophages: Implications for magnetic resonance imaging
Authors: Karin Müller, Jeremy N. Skepper, Tjun Y. Tang, Martin J. Graves, Andrew J. Patterson, Claire Corot, Eric Lancelot, Paul W. Thompson, Andrew P. Brown, Jonathan H. Gillard
Journal: Biomaterials (2008)