tbuckley/cabot-search huggingface dataset:
Evaluation of high-energy phosphate metabolism during cardioplegic arrest and reperfusion: a phosphorus-31 nuclear magnetic resonance study.
Authors: A C Pernot, J S Ingwall, P Menasche, C Grousset, M Bercot, A Piwnica, E T Fossel
Journal: Circulation (1983)

Hypothermic potassium cardioplegia is now commonly used to protect the myocardium during surgically induced ischemia. Because the potassium-related membrane depolarization has been shown to increase calcium influx, we undertook this study to define the effects of varying the calcium content in hyperkalemic perfusates and the effects of using magnesium instead of or in addition to potassium as the arresting agent on the ability of hearts to recover normal function after ischemic arrest. We subjected isolated perfused working rat hearts to 60 minutes of cardioplegic arrest followed by 30 minutes of reperfusion, and measured high-energy phosphate levels every 2 1/2 minutes by phosphorus-31 nuclear magnetic resonance spectroscopy. These data were correlated with postischemic recovery of function. Our results show that potassium cardioplegia may be harmful when the calcium concentration is greater than 1 mM. The kalemic injury is significantly reduced when the calcium content is lowered to 0.25 mM and the greatest extent of preservation is provided by a calcium-poor perfusate (0.25 mM) containing 13 mM magnesium. The beneficial effects of magnesium are not enhanced by subsequent addition of potassium. Close correlations were found between all observed metabolic changes during arrest and the degree of recovery of contractile performance after reperfusion. We conclude that the ability of the myocardium to maintain or resynthesize high-energy phosphate after cardioplegic arrest may be an important determinant of postischemic mechanical performance. These results show that phosphorus-31 nuclear magnetic resonance spectroscopy is a valuable method for evaluating interventions to reduce the severity of ischemic damage.
Clinical and bronchoscopic diagnosis of suspected pneumonia related to AIDS.
Authors: A L Pozniak, K T Tung, C R Swinburn, S Tovey, S J Semple, N M Johnson
Journal: BMJ (1986)

In a series of 25 patients with suspected pneumonia related to the acquired immune deficiency syndrome (AIDS) the first 12 underwent routine fibreoptic bronchoscopy and bronchoalveolar lavage with or without transbronchial biopsy before treatment. Eight were found to have Pneumocystis carinii pneumonia and had typical clinical presentations with a prolonged history of symptoms, including a dry cough, and bilateral diffuse alveolar or interstitial shadowing in chest radiographs. Among the subsequent 13 cases, 11 had similar clinical presentations and were treated with high doses of intravenous co-trimoxazole without bronchoscopy first. Bronchoscopy was performed in those who deteriorated at any stage or failed to improve by the fifth day of treatment. Nine patients recovered and were discharged. In two patients who died P carinii pneumonia was confirmed in one but no diagnosis was made in the other. The early and late survival in both groups of patients was similar. In patients at high risk for AIDS who have clinical features suggestive of P carinii pneumonia starting treatment with intravenous co-trimoxazole is justified. The few patients who deteriorate or fail to respond should undergo bronchoscopy with bronchoalveolar lavage and transbronchial biopsy.
Integrity in the National Resident Matching Program
Authors: Arthur M. Boudreaux
Journal: JAMA (1992)

<h3>To the Editor.</h3> —As chairman of the resident selection committee of a large university anesthesiology residency program, I eagerly awaited this year's match results. As usual, there were several individuals we strongly anticipated matching, who selected different programs. These candidates communicated with our faculty and/or residents by letter or phone expressing strong interest in our program. Most wrote several letters and phoned making statements about their intention to rank our program first on their match list. Each year we are amazed at the manipulative behavior of some of our applicants. They often don't tell the truth. The intensely competitive nature of obtaining postgraduate training may be their justification. Like competing for employment in the business world, they will tell their prospective employer anything just to get the job! The fear and embarrassment of not "matching" is a compelling motivation. Part of our duty as physician educators is to be role
Dramatic response to ASP-3026 in patient with highly aggressive pulmonary inflammatory myofibroblastic tumor harboring ALK rearrangement
Authors: A. Ono, H. Murakami, K. Wakuda, T. Taira, H. Kenmotsu, T. Naito, Y. Ohde, M. Endo, T. Nakajima, T. Takahashi
Journal: Annals of Oncology (2015)
Biologic and Immunologic in Vivo and In Vitro Studies with Biosynthetic Human Insulin
Authors: Konrad Federlin, Heinrich Laube, Hans Georg Velcovsky
Journal: Diabetes Care (1981)

A preliminary study was performed to estimate the effect of biosynthetic human insulin (BHI) produced by the Eli Lilly Company in comparison with purified pork insulin (PPI) from the same manufacturer. Immunologic studies were done using an intradermal skin test with both insulins and in vitro studies binding with sera containing preformed antibodies against bovine and pork insulin. The studies were undertaken in eight healthy volunteers aged 24–31 yr. Insulin was given subcutaneously in an amount of 0.1 U/kg and 3 days later intravenously in an amount of 0.03 U/kg injected slowly over 1 min. Blood glucose, insulin, C-peptide, and growth hormone were measured at different times between 0 and 360 min. It was shown that BHI and PPI behaved similarly in lowering blood glucose, suppressing C-peptide, and increasing growth hormone via hypoglycemic action. After s.c. injection, BHI was found to reach higher serum concentrations after 60 min than PPI. Correspondingly, the blood glucose curve was significantly lower after BHI than after PPI. This difference was not observed after the i.v. application of both forms of insulin.
Rapid one step urine test for human chorionic gonadotrophin in evaluating suspected complications of early pregnancy.
Authors: J C Kingdom, T Kelly, A B MacLean, E J McAllister
Journal: BMJ (1991)

To determine the ability of a sensitive one step urine test to detect human chorionic gonadotrophin in women with suspected complications of early pregnancy.Test on women presenting to accident and emergency department with gynaecological problems over six months. Results were validated using a quantitative assay for human chorionic gonadotrophin in serum and urine.Accident and emergency department and gynaecology wards of a university teaching hospital.130 unselected women.Detection of human chorionic gonadotrophin by one step test, presence of ectopic pregnancy, and results of quantitative analysis of chorionic gonadotrophin in serum and urine.79 women had a positive urine test result and 51 a negative result. All 12 women with ectopic pregnancy had a positive test result, although urinary concentration varied from 191 IU/l to 47,800 IU/l. Only one woman, who had a faintly positive result, was found not to be pregnant on subsequent examination. The sensitivity and negative predictive values of the urine test were 100% respectively. 33 women were sent home from the accident and emergency department with normal clinical findings after a negative urine test result. All these women had undetectable concentrations of chorionic gonadotrophin in matched samples of urine and serum.A simple, rapid one step test for chorionic gonadotrophin should be available for the initial evaluation of emergency gynaecological problems. The additional cost of the test is offset by not admitting those patients whose clinical findings are normal and who have a negative urine test result and by reducing the number of women requiring quantitative assays of chorionic gonadotrophin.
The contribution of Nox4 to NADPH oxidase activity in mouse vascular smooth muscle
Authors: S ELLMARK, G DUSTING, M NGTANGFUI, N GUZZOPERNELL, G DRUMMOND
Journal: Cardiovascular Research (2004)

NADPH oxidases are important sources of reactive oxygen species (ROS) in the vasculature. In phagocytic cells, the catalytic subunit of NADPH oxidase is a glycoprotein, gp91phox. However, vascular smooth muscle cells (VSMCs), which show prominent NADPH oxidase activity, lack gp91phox. Hence, we examined the role of Nox4, a gp91phox homologue, in superoxide production in mouse-cultured VSMCs.Incubation of VSMCs with NADPH increased ROS production whether detected by lucigenin-enhanced chemiluminescence or dichlorofluorescein. Superoxide production was inhibited by the NADPH oxidase inhibitors, diphenyleneiodonium and apocynin, but not by inhibitors of other potential sources of superoxide. In unstimulated VSMCs, phosphorothioate antisense oligonucleotides against Nox4 down-regulated mRNA expression of the subunit by 65% and attenuated superoxide production by 41% without affecting Nox1 expression. Interleukin-1beta (IL-beta) thrombin and platelet-derived growth factor (PDGF) also reduced Nox4 mRNA expression after 3 h without affecting Nox1 levels. Of these stimuli, only IL-beta reduced superoxide, but this effect was more rapid (< or =30 min) than its actions on Nox4.Under resting conditions, NADPH oxidase activity in VSMCs is largely dependent upon Nox4 expression. Proinflammatory mediators down-regulated Nox4 but did not affect Nox1 expression, so other factors must compensate to regulate superoxide production.
Relief of the Pruritus of Jaundice with a Bile-Acid Sequestering Resin
Authors: James B. Carey
Journal: JAMA (1961)

The purpose of this study was to determine whether a resin capable of removing bile acids from the enterohepatic circulation by forming a nonabsorbable complex with them in the gut lumen would be effective in lowering the serum bile acid concentration and relieving the pruritus. The resin was fed to 4 jaundiced patients with high serum bile acid concentrations and intense pruritus. In each patient the serum bile acid concentrations were lowered and pruritus was relieved. In 2 of these patients, withholding the resin was associated with a prompt rise in serum bile acids and return of pruritus; refeeding the resin again lowered serum bile acids and relieved pruritus. It was thus observed that correction of the hyperbileacidemia of pruritic jaundice by resin feeding is associated with relief of the pruritus.
Pragmatic randomised trials using routine electronic health records: putting them to the test
Authors: T.-P. v. Staa, B. Goldacre, M. Gulliford, J. Cassell, M. Pirmohamed, A. Taweel, B. Delaney, L. Smeeth
Journal: BMJ (2012)

What to prescribe for a patient in general practice when the choice of treatments has a limited evidence base? <b>Tjeerd-Pieter van Staa and colleagues</b> argue that using electronic health records to enter patients into randomised trials of treatments in real time could provide the answer
The stimulant effect of drugs on indocyanine green clearance by the liver
Authors: V. Melikian, J. D. Eddy, A. Paton
Journal: Gut (1972)

The rate of removal of a standard dose of 25 mg indocyanine green was studied in 67 patients at the bedside using dichromatic ear densitometry. The determination of the percentage disappearance rate per minute and the half life of the dye permitted separation of patients into three groups: those with normal liver function, those with liver damage, and a group taking opiates (9), anticonvulsants (8), phenylbutazone (2), haloperidol (1), and nitrofurantoin (1). The last group showed enhanced clearance of indocyanine green from the circulation.
957. Effect of Ligand Binding Affinity and Receptor Density in Relation to Biology of Retargeted Viruses
Authors: Kosei Hasegawa, Takafumi Nakamura, James D. Marks, Stephen J. Russell, Kah-Whye Peng
Journal: Molecular Therapy (2006)

The measles virus display platform technology is highly flexible and can accommodate insertions of single-chain antibodies (scFvs) into the viral attachment protein without significant compromise to virus infectivity and cytopathic effects of cell fusion. Using the measles display platform, we investigated the role of ligand affinity and receptor density in the biology of retargeted viruses and sought to evaluate the role of these parameters in modulating efficiency of virus-cell fusion and cell-to-cell fusion. Fully retargeted measles viruses that interact exclusively with the Her-2/neu (Her-2) receptor were used. A panel of 6 viruses displaying scFvs with affinities for Her-2 in the range of 10-6 to 10-11 M was generated. All viruses were rescued and infected cells via the Her-2 receptor with different efficiencies and in a manner that is dependent on receptor density on the target cells. Syncytia were undetectable with the low affinity (10-6 and 10-7 M) scFvs but became apparent above the threshold of 10-8 M. Viruses displaying the high affinity scFvs can overcome the limitation imposed by low receptor density and were significantly more efficient in inducing intercellular fusion in MDA-MB-231 cells that express only 3000 copies of Her-2/cell. While these 6 viruses produced equivalent cell associated virions, release of viral progeny from the infected cells was progressively poorer with increase in scFv affinities, indicating that there is an optimal affinity for target receptors. Potential differences in kinetics of virus entry and cell fusion are currently being evaluated in conjunction with in vivo targeting studies. Results in this work have important implications for the selection of the target tumor antigen and the design of future generations of retargeted measles viruses.
Regulation of the gp80 and gp130 subunits of the IL-6 receptor by sex steroids in the murine bone marrow.
Authors: S C Lin, T Yamate, Y Taguchi, V Z Borba, G Girasole, C A O'Brien, T Bellido, E Abe, S C Manolagas
Journal: Journal of Clinical Investigation (1997)

Both estrogen and androgen exert their antiosteoporotic effects, at least in part, by inhibiting IL-6 production, thereby suppressing osteoclastogenesis. Several observations, however, suggest that besides increased IL-6 production, sensitivity of the osteoclastogenic process to this cytokine is altered after ovariectomy. Based on this and evidence that the ligand-binding subunit of the IL-6 receptor (gp80) is a limiting factor for the actions of IL-6 on bone, we hypothesized that sex steroids regulate expression of the IL-6 receptor as well. We report that 17beta-estradiol or dihydrotestosterone in vitro decreased the abundance of the gp80 mRNA as well as the mRNA of the signal-transducing subunit of the IL-6 receptor (gp130) in cells of the bone marrow stromal/osteoblastic lineage, and also decreased gp130 protein levels. These effects did not require new protein synthesis. In contrast to sex steroids, parathyroid hormone stimulated gp130 expression; this effect was opposed by sex steroids. Consistent with these findings, ovariectomy in mice caused an increase in expression of gp80, gp130, and IL-6 mRNAs in ex vivo bone marrow cell cultures as determined by quantitative reverse transcription (RT)-PCR, and confirmed on an individual cell basis using in situ RT-PCR. The demonstration of increased expression of the IL-6 receptor after loss of sex steroids provides an explanation for why IL-6 is important for skeletal homeostasis in the sex steroid-deficient, but not replete, state.
Bile acids and colonic motility in the rabbit and the human.
Authors: W O Kirwan, A N Smith, W D Mitchell, J D Falconer, M A Eastwood
Journal: Gut (1975)

Colonic motor activity was initiated by infusions of bile salts into the caecum or rectum of the anaesthetized rabbit. Primary bile acids were examined proximally and distally in the colon and elicited marked motor responses. Sinc dihydroxy bile acids are known to be potent inhibitors of electrolyte and water absorption in the colon, the secondary bile acid deoxycholic acid, the dihydroxyl compound most related to cholic acid which is the main bile acid in the rabbit, was examined distally and was also active, but to a lesser extent than cholic acid conjugates in this species. In man, a relationship was found between the faecal bile acid excretion and colonic motility: the introduction of bile acids directly into the human sigmoid colon and rectum also stimulated colonic motility. In man, the dihydroxy compound chenodeoxycholic acid was slightly more active than conjugates of cholic acid.
Diazoxide Opens the Mitochondrial Permeability Transition Pore and Alters Ca <sup>2+</sup> Transients in Rat Ventricular Myocytes
Authors: Hideki Katoh, Nobuhiro Nishigaki, Hideharu Hayashi
Journal: Circulation (2002)

The mitochondrial K(ATP) channel (mitoK(ATP)) has been implicated as an end effector or trigger of ischemic preconditioning (IP). Although a mitoK(ATP) opener, diazoxide, mimics IP, mechanisms for the cardioprotective action remain unclear.We measured Ca2+ transients (CaTs) and mitochondrial inner membrane potential (Deltapsi(m)) with confocal microscopy and the fluorescent probes fluo-4 and tetramethylrhodamine ethyl ester perchlorate in rat ventricular myocytes. Diazoxide increased the amplitudes and diastolic levels of CaTs dose dependently. The effects of diazoxide on CaTs were inhibited by the mitoK(ATP) antagonist sodium 5-hydroxydecanoic acid (100 micromol/L), whereas application of diazoxide caused little change in Deltapsi(m). After sarcoplasmic reticulum function was disabled with ryanodine and thapsigargin, the effects of diazoxide on CaTs were still observed. The opening of the mitochondrial permeability transition pore was monitored with fluorescent calcein. Diazoxide accelerated the leakage of calcein from mitochondrial matrix (16% of control; P<0.05), and this effect was inhibited by cyclosporin A (2 micromol/L). Cyclosporin A also abolished the effects of diazoxide on CaTs. Diazoxide oxidized flavoprotein fluorescence reversibly, and this effect was partially blunted by cyclosporin A (by 24%; P<0.05).We conclude that in rat ventricular myocytes, diazoxide modulates the opening of the mitochondrial permeability transition pore, resulting in an increase in CaTs independent of the changes in Deltapsi(m). The action of diazoxide on the mitochondrial permeability transition pore also affects the mitochondrial redox state.
Chagas disease of the colon and rectum
Authors: I. P. Todd, N. H. Porter, B. C. Morson, B. Smith, C. A. Friedmann, R. A. Neal
Journal: Gut (1969)

Chagas disease is a rare condition in patients anywhere but in Central and Latin America. This case is therefore reported because the patient was born in Britain and spent only a short time in an area where Chagas disease is endemic. It is believed that this patient is the first case of Chagas disease to be treated in Britain. Chagas disease causes a generalized degeneration of autonomic ganglia and usually presents as megaoesophagus or megacolon. The disease may also cause the heart to enlarge followed by cardiac failure.
VENOUS BLOOD-PRESSURE AS INFLUENCED BY THE DRUGS EMPLOYED IN CARDIOVASCULAR THERAPY
Authors: JOSEPH A. CAPPS
Journal: JAMA (1913)

When one considers the enormous amount of attention that has been directed to the changes in arterial pressure, it appears that the study of the venous pressure has been neglected. There has been no neglect, however, in the study of the waves in the venous pulse. It is fair to say that the investigations of sphygmographic tracings of the venous pulse have thrown as much light on cardiac and circulatory phenomena as have those of tracings of the arterial pulse. Is it not possible that a knowledge of variations in venous pressure may prove as valuable as that of variations in arterial pressure? Venous pressure has excited the interest of physiologists with special reference to vasomotor influences. It is well known that the arteries of the body are supplied by vasomotor nerves which largely determine the volume and rate of flow of blood within them. Formerly the rôle of the
UK government scraps mental health bill
Authors: Clare Dyer
Journal: BMJ (2006)

The UK government is to scrap a controversial draft bill to reform mental health law in England and Wales after eight years of opposition by psychiatrists, lawyers, and mental health charities. As set out by the BMJ in February (2006;332: 444, 25 Feb), the lengthy and complex draft mental health bill is to be dropped and a much shorter bill introduced to amend the existing Mental Health Act, which dates back to 1983. The decision to scrap the draft bill was welcomed by campaigners, …
Transient isolated brainstem symptoms preceding posterior circulation stroke: a population-based study
Authors: Nicola LM Paul, Michela Simoni, Peter M Rothwell
Journal: The Lancet Neurology (2012)

Transient isolated brainstem symptoms (eg, isolated vertigo, dysarthria, diplopia) are not consistently classified as transient ischaemic attacks (TIAs) and data for prognosis are limited. If some of these transient neurological attacks (TNAs) are due to vertebrobasilar ischaemia, then they should be common during the days and weeks preceding posterior circulation strokes. We aimed to assess the frequency of TNAs before vertebrobasilar ischaemic stroke.We studied all potential ischaemic events during the 90 days preceding an ischaemic stroke in patients ascertained within a prospective, population-based incidence study in Oxfordshire, UK (Oxford Vascular Study; 2002-2010) and compared rates of TNA preceding vertebrobasilar stroke versus carotid stroke. We classified the brainstem symptoms isolated vertigo, vertigo with non-focal symptoms, isolated double vision, transient generalised weakness, and binocular visual disturbance as TNAs in the vertebrobasilar territory; atypical amaurosis fugax and limb-shaking as TNAs in the carotid territory; and isolated slurred speech, migraine variants, transient confusion, and hemisensory tingling symptoms as TNAs in uncertain territory.Of the 1141 patients with ischaemic stroke, vascular territory was categorisable in 1034 (91%) cases, with 275 vertebrobasilar strokes and 759 carotid strokes. Isolated brainstem TNAs were more frequent before a vertebrobasilar stroke (45 of 275 events) than before a carotid stroke (10 of 759; OR 14·7, 95% CI 7·3-29·5, p<0·0001), particularly during the preceding 2 days (22 of 252 before a vertebrobasilar stroke vs two of 751 before a carotid stroke, OR 35·8, 8·4-153·5, p<0·0001). Of all 59 TNAs preceding (median 4 days, IQR 1-30) vertebrobasilar stroke, only five (8%) fulfilled the National Institute of Neurological Disorders and Stroke (NINDS) criteria for TIA. The other 54 cases were isolated vertigo (n=23), non-NINDS binocular visual disturbance (n=9), vertigo with other non-focal symptoms (n=10), isolated slurred speech, hemisensory tingling, or diplopia (n=8), and non-focal events (n=4). Only 10 (22%) of the 45 patients with isolated brainstem TNAs sought medical attention before the stroke and a vascular cause was suspected by their physician in only one of these cases.In patients with definite vertebrobasilar stroke, preceding transient isolated brainstem symptoms are common, but most symptoms do not satisfy traditional definitions of TIA. More studies of the prognosis of transient isolated brainstem symptoms are required.Wellcome Trust, UK Medical Research Council, Dunhill Medical Trust, Stroke Association, National Institute for Health Research (NIHR), Thames Valley Primary Care Research Partnership, and the NIHR Biomedical Research Centre, Oxford.