tbuckley/cabot-search huggingface dataset:
ATP-Dependent Potassium Channel in Rat Cardiomyocytes Is Blocked by Lidocaine
Authors: A. Olschewski, M.E. Bräu, H. Olschewski, G. Hempelmann, W. Vogel
Journal: Circulation (1996)

Background During myocardial ischemia, lidocaine has favorable antiarrhythmic properties. Malignant arrhythmias result from heterogeneity between ischemic and nonischemic regions in extracellular potassium concentration and action potential duration. These effects have been attributed to the activation of ATP-dependent potassium (K ATP ) channels. In this study, we investigated the action of lidocaine on the K ATP channels to test the possible link between the antiarrhythmic properties of lidocaine and its action on the K ATP channel. Methods and Results The patch-clamp technique was employed on enzymatic dissociated cardiomyocytes of adult rats. Lidocaine was applied to the outer side of excised membrane patches by means of a multibarrel perfusion system. Lidocaine reversibly blocked the mean current of the K ATP channels in a concentration-dependent manner (IC 50 =43±4.7 μmol/L, E=0 mV, n=6), while the amplitude of the single-channel current remained unchanged. The half-maximum blocking concentration corresponds to the therapeutic range for the antiarrhythmic application of a lidocaine bolus in humans. Conclusions The open probability but not the conductance of the K ATP channel in the membrane of rat cardiomyocytes is blocked by lidocaine. This action may explain, in part, the favorable antiarrhythmic properties of lidocaine during acute myocardial ischemia.
The Witch Doctor: Memoirs of a Partisan
Authors: Harriet S. Meyer
Journal: JAMA (1984)

Eighteen months as a German prisoner of war were only the beginning.  InThe Witch Doctor, Dr Michael Temchin tells of his life during the Second World War. Already a physician, he was in the Polish Army when captured by the Germans in 1939. In 1940, he escaped from a labor camp, lived for a while in the Warsaw ghetto, then fled to Grabowiec. When the Jews of that town were rounded up the next year, he jumped off the train bound for a concentration camp and became a bandit in the Polish countryside. Gradually, he allied with others in hiding, then joined with partisans, and ultimately became chief medical officer of the People's Army. Dr Temchin survived the war and eventually practiced medicine in New York.  Znachor (Witch Doctor) was the name the author came to be known by. Throughout this memoir, Temchin gives evidences of the special accord
Commentary on the paper of Carlsson et al in this issue
Authors: S. REES
Journal: Cardiovascular Research (1993)

Journal Article Commentary on the paper of Carlsson et al in this issue Get access SIAN REES SIAN REES Department of Pharmacology, King's College, Manresa Rd, London SW3, United Kingdom Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 12, December 1993, Pages 2285–2286, https://doi.org/10.1093/cvr/27.12.2285a Published: 01 December 1993
Arterial Calcification Simulating Aneurysm
Authors: Helen C. Redman
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Abdominal aortic aneurysms are often excised following the discovery of a pulsatile abdominal mass associated with the radiographic finding of vascular calcification in the abdomen. This calcification, usually seen to the left of the spine, is often associated with a medial soft-tissue mass. The calcification is assumed to be in an aneurysmally dilated abdominal aorta. The pulsatile mass is considered confirmatory evidence of an abdominal aortic aneurysm. Two cases of superior mesenteric arterial calcification which simulated aortic aneurysm in patients with a pulsatile abdominal mass have been seen recently. These cases are reported to emphasize the importance of preoperative angiography to confirm the actual existence of an aneurysm. <h3>Report of Cases:—</h3> Routine physical examination on a 68-year-old woman with chronic brain syndrome revealed a pulsatile midline abdominal mass without bruit located below the umbilicus. This was felt to represent an aortic aneurysm clinically. Plain films of the
Metabolic adjustments to acute heart work: observations in the isolated perfused rat heart
Authors: L. H. Opie, P. Owen, K. R. L. Mansford
Journal: Cardiovascular Research (1971)

Journal Article Metabolic adjustments to acute heart work: observations in the isolated perfused rat heart Get access L. H. Opie, L. H. Opie From the M.R.C. Cardiovascular Research Unit, Department of Medicine, Hammersmith Hospital, London, and the Department of Biochemistry, Imperial College of Science and Technology, London Search for other works by this author on: Oxford Academic PubMed Google Scholar Patricia Owen, Patricia Owen From the M.R.C. Cardiovascular Research Unit, Department of Medicine, Hammersmith Hospital, London, and the Department of Biochemistry, Imperial College of Science and Technology, London Search for other works by this author on: Oxford Academic PubMed Google Scholar K. R. L. Mansford K. R. L. Mansford From the M.R.C. Cardiovascular Research Unit, Department of Medicine, Hammersmith Hospital, London, and the Department of Biochemistry, Imperial College of Science and Technology, London Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 5, Issue supp1, July 1971, Pages 87–95, https://doi.org/10.1093/cvr/5.supp1.87 Published: 01 July 1971
Playing hide and seek with poorly tasting paediatric medicines: Do not forget the excipients
Authors: Jennifer Walsh, Anne Cram, Katharina Woertz, Joerg Breitkreutz, Gesine Winzenburg, Roy Turner, Catherine Tuleu
Journal: Advanced Drug Delivery Reviews (2014)

The development of paediatric medicines can be challenging since this is a diverse patient population with specific needs. For example, the toxicity of excipients may differ in children compared to adults and children have different taste preferences. Acceptable palatability of oral paediatric medicinal products is of great importance to facilitate patient adherence. This has been recognised by regulatory authorities and so is becoming a key aspect of paediatric pharmaceutical development studies. Many active pharmaceutical ingredients (APIs) have aversive taste characteristics and so it is necessary to utilise taste masking techniques to improve the palatability of paediatric oral formulations. The aim of this review is to provide an overview of different approaches to taste masking APIs in paediatric oral dosage forms, with a focus on the tolerability of excipients used. In addition, where possible, the provision of examples of some marketed products is made.
Lentiviral Vectors Bearing the Cardiac Promoter of the Na+-Ca2+ Exchanger Report Cardiogenic Differentiation in Stem Cells
Authors: Andreas S Barth, Eddy Kizana, Rachel R Smith, John Terrovitis, Peihong Dong, Michelle K Leppo, Yiqiang Zhang, Junichiro Miake, Eric N Olson, Jay W Schneider, M Roselle Abraham, Eduardo Marbán
Journal: Molecular Therapy (2008)

Cardiosphere-derived resident cardiac stem cells (CDCs) are readily isolated from adult hearts and confer functional benefit in animal models of heart failure. To study cardiogenic differentiation in CDCs, we developed a method to genetically label and selectively enrich for cells that have acquired a cardiac phenotype. Lentiviral vectors achieved significantly higher transduction efficiencies in CDCs than any of the nine adeno-associated viral (AAV) serotypes tested. To define the most suitable vector system for reporting cardiogenic differentiation, we compared the cell specificity of five commonly-used cardiac-specific promoters in the context of lentiviral vectors. The promoter of the cardiac sodium-calcium exchanger (NCX1) conveyed the highest degree of cardiac specificity, as assessed by transducing seven cell types with each vector and measuring fluorescence intensity by flow cytometry. NCX1-GFP-positive CDC subpopulations, demonstrating prolonged expression of a variety of cardiac markers, could be isolated and expanded in vitro. Finally, we used chemical biology to validate that lentiviral vectors bearing the cardiac NCX1-promoter can serve as a highly accurate biosensor of cardiogenic small molecules in stem cells. The ability to accurately report cardiac fate and selectively enrich for cardiomyocytes and their precursors has important implications for drug discovery and the development of cell-based therapies.
Phase I trial of UCN-01 in combination with topotecan in patients with advanced solid cancers: a Princess Margaret Hospital Phase II Consortium study
Authors: S.J. Hotte, A. Oza, E.W. Winquist, M. Moore, E.X. Chen, S. Brown, G.R. Pond, J.E. Dancey, H.W. Hirte
Journal: Annals of Oncology (2005)
NADH-dehydrogenase Type-2 Suppresses Irreversible Visual Loss and Neurodegeneration in the EAE Animal Model of MS
Authors: Venu Talla, Hong Yu, Tsung-Han Chou, Vittorio Porciatti, Vince Chiodo, Sanford L Boye, William W Hauswirth, Alfred S Lewin, John Guy
Journal: Molecular Therapy (2013)

To address mitochondrial dysfunction that mediates irreversible visual loss and neurodegeneration of the optic nerve in the experimental autoimmune encephalomyelitis (EAE) animal model of multiple sclerosis (MS), mice sensitized for EAE were vitreally injected with self-complementary adenoassociated virus (scAAV) containing the NADH-dehydrogenase type-2 (NDI1) complex I gene that quickly expressed in mitochondria of almost all retinal ganglion cells (RGCs). Visual function assessed by pattern electroretinograms (PERGs) reduced by half in EAE showed no significant reductions with NDI1. Serial optical coherence tomography (OCT) revealed significant inner retinal thinning with EAE that was suppressed by NDI1. Although complex I activity reduced 80% in EAE was not improved by NDI1, in vivo fluorescent probes indicated mitochondrial oxidative stress and apoptosis of the EAE retina were reduced by NDI1. Finally, the 42% loss of axons in the EAE optic nerve was ameliorated by NDI1. Targeting the dysfunctional complex I of EAE responsible for loss of respiration, mitochondrial oxidative stress and apoptosis may be a novel approach to address neuronal and axonal loss responsible for permanent disability that is unaltered by current disease modifying drugs for MS that target inflammation.
Hydroxychloroquine and lupus pregnancy: review of a series of 36 cases.
Authors: N M Buchanan, E Toubi, M A Khamashta, F Lima, S Kerslake, G R Hughes
Journal: Annals of the Rheumatic Diseases (1996)

To study maternal and fetal outcome of pregnancy in patients with lupus who were exposed to hydroxychloroquine (HCQ).The case records of women (n = 33) exposed to HCQ during their pregnancies (n = 36) and of 53 control patients from a single lupus pregnancy centre were reviewed to determine lupus activity, obstetric experience, and infant outcome.HCQ was not apparently teratogenic. Lupus activity and obstetric outcome in the two groups were similar.HCQ continuation is probably safe during pregnancy in patients with lupus, but there is no obvious advantage in commencing treatment.
Abstract P6-06-24: Intact p53 can predict more hormonal therapy benefit in invasive breast cancer: Evaluation of interactions between immunohistochemical p53 status and adjuvant therapy
Authors: JW Lee, HJ Kim, BH Son, SH Ahn
Journal: Cancer Research (2013)

Abstract Background: To confirm the prognostic and predictive values of p53 accumulation, particularly in invasive breast cancer patients sorted according to subgroup based on immunohistochemical hormone receptor (HR) and HER2 status. Methods: A total of 15,598 immunohistochemical data for p53, ER, PgR, and HER2 were retrospectively retrieved from the web-based database of the Korean Breast Cancer Society. Overall survival (OS) and breast cancer-specific survival (BCSS) were calculated and compared with the Kaplan-Meier method with log-rank test. Multivariate analyses were performed using a stratified Cox proportional hazard regression model. A model evaluating interactions between p53 and both hormonal therapy and chemotherapy was used to determine the treatment benefit from both modalities. Results: Prognostic value of p53 was most significant in the HR+/HER2- subgroup for OS and BCSS, with hazard ratios of 1.44 (95% CI, 1.08-1.93) and of 1.47 (95% CI, 1.09-1.99). The hazard ratios for p53 overexpression had borderline significance in the HR+/HER2+, and were invalid in the HR-/HER2+ and HR-/HER2- subgroups. The model with interaction terms revealed that hormonal therapy significantly interacts with p53 status (p = .002 and .007 for OS and BCSS), resulting in an insignificant prognostic value of p53 status (p = .268 and .296 for OS and BCSS). An interaction between chemotherapy and p53 status was not found in this model. Conclusion: p53 overexpression has independent prognostic value, particularly in the HR+/HER2- invasive breast cancer, which is most likely caused by differential treatment benefits from hormonal therapy depending on p53 status. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-24.
Treatment of Habitual Drunkards
Authors: J. W. Eastwood
Journal: BMJ (1875)

<h3>SUMMARY:</h3> Forced exhalation against a closed glottis, known as the Valsalva maneuver, is an important clinical diagnostic and therapeutic tool due to its physiologic effects. Several unique conditions and anatomic changes can occur with repetitive or acute changes in pressure from the Valsalva maneuver. We will discuss and review various pertinent head and neck imaging cases with findings resulting from induced pressure gradients, including the Valsalva maneuver. Additionally, we will demonstrate the diagnostic utility of the Valsalva maneuver in head and neck radiology.
Optimisation of positive and expiratory pressure for maximal delivery of oxygen to tissues using oesophageal Doppler ultrasonography.
Authors: M. Singer, D. Bennett
Journal: BMJ (1989)

OBJECTIVE--To assess oesophageal Doppler ultrasonography as a convenient means of optimising positive end expiratory pressure for maximal delivery of oxygen to tissues. DESIGN--Measurements of blood flow, arterial oxygen saturation, and cardiac output by thermodilution (when available) at baseline and at 20-30 minutes after each incremental increase (2.5-5.0 cm H2O) in positive and expiratory pressure to a maximum of 20.0 cm H2O. If the cardiac output fell by more than 15% measurements were repeated after stepwise decreases in positive end expiratory pressure. No other manoeuvre such as endotracheal suction or changing ventilator settings, drug or fluid dosage, or the patient9s position was performed for at least one hour before the start of the study or during it. SETTING--Intensive care unit. PARTICIPANTS--10 Patients being mechanically ventilated for acute respiratory failure who had stable haemodynamic and blood gas values and required a fractional inspired oxygen concentration of greater than or equal to 0.45. They were assessed on a total of 11 occasions. INTERVENTIONS--Incremental increases in positive end expiratory pressure followed when indicated by stepwise decreases. END POINT--The positive end expiratory pressure providing maximal delivery of oxygen to tissues. MEASUREMENTS and MAIN RESULTS--Arterial oxygen saturation increased with positive end expiratory pressure in all patients by an average of 6.1%. In nine of the 11 studies, however, cardiac output fell by 15% to 30% after the second increment. On the two other occasions cardiac output and oxygen delivery rose by up to 54%. Positive end expiratory pressure was decreased on seven occasions; there was considerable individual variation in the time taken for cardiac output to rise and arterial oxygen saturation to fall. In six patients good agreement was seen between the results from Doppler ultrasonography and thermodilution, the mean of the differences being -0.3% with narrow limits of agreement (-14.4% to 13.9%). CONCLUSIONS--Oesophageal Doppler ultrasonography is a rapid, safe, and reliable technique for optimising positive end expiratory pressure to obtain maximal delivery of oxygen to tissues. The results show the need to consider haemodynamic consequences when altering positive end expiratory pressure.
Soluble interleukin 2 receptor in atopic eczema.
Authors: G. B. Colver, J. A. Symons, G. W. Duff
Journal: BMJ (1989)

OBJECTIVE--To determine whether serum soluble interleukin 2 receptor concentrations are related to disease activity in atopic eczema. DESIGN--Single cohort longitudinal study with controls. SETTING--Outpatient and general medicine departments in secondary referral centre. PATIENTS--Of 15 patients aged 17-57 with severe atopic eczema, all with acute exacerbations of disease, 13 were admitted to hospital and two treated as outpatients until the skin lesions had resolved or greatly improved. Nineteen controls gave single blood samples. INTERVENTIONS--Daily skin dressing with betamethasone valerate (0.025%) and ichthammol paste and tubular dressings. END POINT--Resolution of or considerable improvement in skin lesions. MEASUREMENTS AND MAIN RESULTS--Enzyme linked immunosorbent assays (ELISA) were used to measure serum soluble interleukin 2 receptor concentrations in blood samples taken on admission, at intervals subsequently, and on discharge. Clinical scores of disease activity were also made. Median concentrations on admission were significantly higher (770 U/ml) in the patients than the controls (300 U/ml). Concentrations fell significantly during treatment. In 25 assessments made at different times in 13 patients serum soluble interleukin 2 receptor concentration correlated significantly (R = 0.73) with clinical disease activity. CONCLUSIONS--Cellular immunopathogenic mechanisms contribute to atopic eczema. Immune activation can be measured in atopic eczema by measurements of soluble interleukin 2 receptor, and this should facilitate assessment of response to treatment.
Military Medicine in the Middle East
Authors: E. Bulmer
Journal: BMJ (1943)

A plan of treatment for infantile diarrhoea and vomiting which has worked with encouraging results is put forward as a basis for use by those in charge of sick infants.One hundred infants were treated by this method, with a mortality of 23 %'.Certain interesting figures of prognostic value are recorded, including the high death rate of 32.6%0 in infants developing the disease in hospital compared with those developing it at home.In view of this and the recorded high mortality in institutional epidemics, measures for the prevention of the disease in hospital and nurseries are given.Adequate treatment demands team-work and probably presents as highly skilled a form of nursing as any in diseases of children. REFERENCES
How Robust Are "Isolation with Migration" Analyses to Violations of the IM Model? A Simulation Study
Authors: J. L. Strasburg, L. H. Rieseberg
Journal: Molecular Biology and Evolution (2009)

Methods developed over the past decade have made it possible to estimate molecular demographic parameters such as effective population size, divergence time, and gene flow with unprecedented accuracy and precision. However, they make simplifying assumptions about certain aspects of the species' histories and the nature of the genetic data, and it is not clear how robust they are to violations of these assumptions. Here, we use simulated data sets to examine the effects of a number of violations of the "Isolation with Migration" (IM) model, including intralocus recombination, population structure, gene flow from an unsampled species, linkage among loci, and divergent selection, on demographic parameter estimates made using the program IMA. We also examine the effect of having data that fit a nucleotide substitution model other than the two relatively simple models available in IMA. We find that IMA estimates are generally quite robust to small to moderate violations of the IM model assumptions, comparable with what is often encountered in real-world scenarios. In particular, population structure within species, a condition encountered to some degree in virtually all species, has little effect on parameter estimates even for fairly high levels of structure. Likewise, most parameter estimates are robust to significant levels of recombination when data sets are pared down to apparently nonrecombining blocks, although substantial bias is introduced to several estimates when the entire data set with recombination is included. In contrast, a poor fit to the nucleotide substitution model can result in an increased error rate, in some cases due to a predictable bias and in other cases due to an increase in variance in parameter estimates among data sets simulated under the same conditions.
IKK mediates ischemia-induced neuronal death
Authors: Oliver Herrmann, Bernd Baumann, Rossana de Lorenzi, Sajjad Muhammad, Wen Zhang, Jens Kleesiek, Max Malfertheiner, Martin Köhrmann, Ioana Potrovita, Ira Maegele, Cordian Beyer, James R Burke, Mazahir T Hasan, Hermann Bujard, Thomas Wirth, Manolis Pasparakis, Markus Schwaninger
Journal: Nature Medicine (2005)
Leflunomide and hypertension
Authors: B Rozman
Journal: Annals of the Rheumatic Diseases (2002)

Blockade of tumour necrosis factor alpha (TNFα) using infliximab, a chimeric monoclonal antibody against TNFα, is an effective treatment in rheumatoid arthritis and Crohn's disease. 1 2 Sifikakis reported success using infliximab in sight threatening Behçet's disease. 3 A preliminary study has also reported clinical improvements in the primary systemic vasculitis, Wegener's granulomatosis, with the soluble TNFα receptor etanercept. 4 The benefit of lenercept, a soluble p55 TNFα receptor fusion protein, on digital vasculitis in rheumatoid arthritis has also been reported. 5 We report the compassionate treatment of six patients with refractory vasculitis using infliximab.Diagnoses were Wegener's granulomatosis in three and microscopic polyangiitis in three.Three patients were positive for proteinase-3 antineutrophil cytoplasmic antibodies (PR3-ANCA) and one for myeloperoxidase (MPO)-ANCA.Four were female, with a mean age of 58 years (range 23-77) and mean disease duration of 3.5 years.All had had at least three clinical relapses and had received prolonged treatment with corticosteroids and at least four immunosuppressive drugs.At the time of infliximab treatment the eyes were affected in four patients and the lung in three; in addition, five had profound constitutional symptoms.The mean prednisolone dose was 17 mg.Three intravenous doses of infliximab 200 mg were given at monthly intervals for three months.One patient complained of fatigue, myalgia, and blurred vision 24 hours after the first infusion, which did not recur on rechallenge.Infliximab was otherwise well tolerated.Five patients had remission of their disease, four within two weeks of treatment.This allowed steroid withdrawal in three and reduction by more than 50% in two.Disease activity assessed by the Birmingham Vasculitis Activity Scores (BVAS) improved from a mean of 6.3 to 0.8 at three months (fig 1). 6 One patient receiving continued infliximab for six months relapsed when the treatment interval was extended to two months.Mean falls in erythrocyte sedimentation rate and C reactive protein were 17 mm/1st h and 13 mg/l, respectively.The ANCA status was unchanged.Anti-TNFα treatment heralds a new wave of specifically targeted biological interventions of potential value in the treatment of vasculitis.It offers the hope of improved therapeutic efficacy over current agents and the possibility of reducing exposure to steroids and immunosuppressive drugs.Further studies are warranted to confirm these observations and explore the role of infliximab as a component of initial protocols.. . . . . .