tbuckley/cabot-search huggingface dataset:
Voltage-gated calcium channel currents in human coronary myocytes. Regulation by cyclic GMP and nitric oxide.
Authors: J F Quignard, J M Frapier, M C Harricane, B Albat, J Nargeot, S Richard
Journal: Journal of Clinical Investigation (1997)

Voltage-gated Ca2+ channels contribute to the maintenance of contractile tone in vascular myocytes and are potential targets for vasodilating agents. There is no information available about their nature and regulation in human coronary arteries. We used the whole-cell voltage-clamp technique to characterize Ca2+-channel currents immediately after enzymatic dissociation and after primary culture of coronary myocytes taken from heart transplant patients. We recorded a dihydropyridine-sensitive L-type current in both freshly isolated and primary cultured cells. A T-type current was recorded only in culture. The L- (but not the T-) type current was inhibited by permeable analogues of cGMP in a dose-dependent manner. This effect was mimicked by the nitric oxide-generating agents S-nitroso-N-acetylpenicillamine (SNAP) and 3-morpholinosydnonimine which increased intracellular cGMP. Methylene blue, known to inhibit guanylate cyclase, antagonized the effect of SNAP. Inhibitions by SNAP and cGMP were not additive and seemed to occur through a common pathway. We conclude that (a) L-type Ca2+ channels are the major pathway for voltage-gated Ca2+ entry in human coronary myocytes; (b) their inhibition by agents stimulating nitric oxide and/or intracellular cGMP production is expected to contribute to vasorelaxation and may be involved in the therapeutic effect of nitrovasodilators; and (c) the expression of T-type Ca2+ channels in culture may be triggered by cell proliferation.
Metal smelting plants poison hundreds of Chinese children
Authors: J. Parry
Journal: BMJ (2009)

Lead poisoning has been diagnosed in hundreds of children living near two metal smelting plants in China, say China’s state news agency, Xinhua, and other media in China. 

Of 1016 children living in three villages near the Dongling Lead and Zinc Smelting Company plant in the central Shaanxi province who underwent blood tests to measure lead concentrations, 851 have excessive lead, including 174 serious cases. In one village 236 of the 285 children have lead poisoning. The number of villages where children will be offered free tests has been widened, and tests of adults living in villages closest to the plant have shown dangerously high levels of lead and …
Granulomatous contact dermatitis due to gold earrings
Authors: D.K.B. ARMSTRONG, M.Y. WALSH, J.F. DAWSON
Journal: British Journal of Dermatology (1997)

A young female developed persistent nodules at sites of ear piercing with gold earrings and patch testing demonstrated a positive allergic response to gold sodium thiosulphate. Histological examination of the nodules demonstrated a prominent sarcoidal-type granulomatous tissue reaction. This is in contrast to previous reports of lymphocytoma cutis type histology and was associated with the occurrence of epithelioid granulomata at the site of a strongly positive and long-lasting patch-test reaction.
Record damages are awarded in medical negligence case in India
Authors: N. Choudhuri
Journal: BMJ (2013)

India’s Supreme Court last week ordered the AMRI Hospital in Kolkata and three doctors to pay Rs 60 800 000 (£616 566; €719 918; $990 520) plus interest in compensation to Indian-American doctor Kunal Saha for medical negligence that led to the death of his wife, Anuradha, aged 36, in 1998.

This is the highest compensation ordered by the apex court of India in a case relating to medical negligence.

A Metropolitan Magistrate of the Bankshall Court in Kolkata has also directed that the criminal trial of 17 former members of the West Bengal Medical Council will begin on 10 …
Mechanism of arsenic‐induced inhibition of erythropoiesis in mice
Authors: Bernard S. Morse, Maureen Conlan, Dennis G. Giuliani, Murray Nussbaum
Journal: American Journal of Hematology (1980)

Abstract Anemia accompanies arsenic intoxication in man. The present studies were undertaken to clarify further the effects of arsenic on erythropoiesis. A dose‐related inhibition of red cell 59 Fe incorporation and reticulocyte response was observed in normal mice treated with a single injection of arsenic. Arsenite was approximately two times as inhibitory as arsenate. The effects of arsenic on erythropoietin‐induced erythroid differentiation revealed a significant inhibitory effect on young, proliferating marrow nucleated erythroid precursor cells. More mature, nonproliferating nucleated erythroid cells were resistant to the toxic action of arsenic. A dose‐related inhibitory effect of arsenic on DNA synthesis was observed in fetal liver nucleated erythroid cells incubated with 3 H thymidine. Ineffective erythropoiesis as well as the megaloblastic morphology accompanying aberrant DNA synthesis – manifestations of arsenic toxicity in man – were not evident in the present studies.
ON REMOVAL OF THE CERVICAL SYMPATHETIC IN GLAUCOMA AND OPTIC NERVE ATROPHY.
Authors: JAMES MOORES BALL
Journal: JAMA (1900)

I propose to consider the surgery of the cervical portion of the great sympathetic nerve in certain ocular diseases. European oculists and surgeons have performed sympathectomy for glaucoma and exophthalmic goiter. I have gone further, and in one instance removed the superior cervical ganglion for simple atrophy of the optic nerve. I have performed sympathectomy four times up to July 20, 1899. First the cases will be reported; then the conclusions will be drawn. <h3>CASE 1.—EXCISION OF SYMPATHETIC FOR GLAUCOMA ABSOLUTUM.</h3> Mrs. B. S., aged 36, has had pain in and around the right eye for two months, and examination showed vision in this eye reduced to light perception; tension +3, and the pupil widely dilated. The anterior chamber was shallow, the cornea cloudy and slightly anesthetic, the media slightly cloudy, still allowing the fundus to be seen. The episcleral vessels were enlarged. Circumcorneal injection was present and the optic
Appendicitis Secondary to Metastatic Melanoma
Authors: Mio Kitano, Ajay V. Maker, Brock J. Lanier, David N. Danforth, Udai S. Kammula
Journal: JAMA Surgery (2014)

Malignant melanoma has an unusual propensity to metastasize to the small bowel; however, malignant melanoma with metastatic spread to the appendix presenting as acute appendicitis has rarely been reported. We describe cases of melanoma of the appendix presenting with appendicitis and review our institutional experience with this entity.Medical records were reviewed in patients with melanoma at the National Cancer Institute between January 1, 1953, and December 31, 2010, who underwent appendectomy. Of 5822 cases of melanoma treated at the National Institutes of Health, appendectomies were performed on 31 patients, 2 of whom had acute appendicitis secondary to malignant obstruction and presented with symptoms of vague abdominal pain. Both patients had been heavily pretreated for metastatic melanoma and had multiple sites of intraperitoneal and extraperitoneal disease. On exploratory laparotomy, both patients showed clinical evidence of acute appendicitis, and an appendectomy was performed. Both patients recovered fully from the operation and proceeded to further systemic therapy.Although rare, the diagnosis of appendicitis should be considered in patients with melanoma and acute abdominal pain. Timely surgical intervention may allow palliation and the ability to pursue subsequent systemic treatment.
Effects of Estrogen Replacement Therapies on Mouse Platelet Function and Glycoprotein VI Levels
Authors: Xing-Hong Leng, Wei Zhang, Bernhard Nieswandt, Paul F. Bray
Journal: Circulation Research (2005)

Clinical trials have shown estrogen replacement therapy (ERT) is associated with adverse arterial vascular events. Arterial thrombosis is initiated by platelet activation, but the in vivo effects of estrogens on platelet function are not well understood. We used a murine model of menopause to examine 3 major ERT regimes and test the hypothesis that ERT affects the intrinsic platelet response to agonists. The 3 ERT regimes studied were: (1) oral conjugated equine estrogen (CEE), (2) oral 17-beta estradiol (E2), and (3) subcutaneously implanted E2 (SQ E2). Paired ovariectomized littermates were treated with these regimes or placebo for 21 days. Two platelet agonists, thrombin and the GPVI-specific agonist collagen-related peptide (COL-RP), were used to evaluate platelet reactivity. Among the 3 regimens, (1) oral CEE enhanced platelet reactivity to COL-RP, (2) oral E2 had no effect on platelet reactivity to COL-RP and (3) SQ E2 increased platelet sensitivity to thrombin but lowered reactivity to COL-RP. Thus, the in vivo effects of estrogen on platelet function are agonist specific and dependent on hormone formulation and mode of delivery. The GPVI collagen receptor likely mediated some of these effects, because the ERT regimens induced changes in platelet surface GPVI expression corresponding to the observed platelet activation.
Points from letters: Multiple malignancies
Authors: F. Hartveit
Journal: BMJ (1976)

part-time consultant" is, if successful, always available to his patients and colleagues because the tradition of mixed medical practice has always meant availability as required, a true "whole-time doctor."I realise that I am perhaps over-emphasising the difference, but my reason for this is honourable and refers to a previous letter from my colleagues and myself (8 February, 1975, p 336).There is a difference between a profession and a trade.
Mitochondrial transfer from bone-marrow–derived stromal cells to pulmonary alveoli protects against acute lung injury
Authors: Mohammad Naimul Islam, Shonit R Das, Memet T Emin, Michelle Wei, Li Sun, Kristin Westphalen, David J Rowlands, Sadiqa K Quadri, Sunita Bhattacharya, Jahar Bhattacharya
Journal: Nature Medicine (2012)
Exon 45 Skipping Through U1-snRNA Antisense Molecules Recovers the Dys-nNOS Pathway and Muscle Differentiation in Human DMD Myoblasts
Authors: Valentina Cazzella, Julie Martone, Chiara Pinnarò, Tiziana Santini, Shyam Sundar Twayana, Olga Sthandier, Adele D'Amico, Valeria Ricotti, Enrico Bertini, Francesco Muntoni, Irene Bozzoni
Journal: Molecular Therapy (2012)

Exon skipping has been demonstrated to be a successful strategy for the gene therapy of Duchenne muscular dystrophy (DMD): the rational being to convert severe Duchenne forms into milder Becker ones. Here, we show the selection of U1 snRNA-antisense constructs able to confer effective rescue of dystrophin synthesis in a Δ44 Duchenne genetic background, through skipping of exon 45; moreover, we demonstrate that the resulting dystrophin is able to recover timing of myogenic marker expression, to relocalize neuronal nitric oxide synthase (nNOS) and to rescue expression of miRNAs previously shown to be sensitive to the Dystrophin-nNOS-HDAC2 pathway. Becker mutations display different phenotypes, likely depending on whether the shorter protein is able to reconstitute the wide range of wild-type functions. Among them, efficient assembly of the dystrophin-associated protein complex (DAPC) and nNOS localization are important. Comparing different Becker deletions we demonstrate the correlation between the ability of the mutant dystrophin to relocalize nNOS and the expression levels of two miRNAs, miR-1 and miR29c, known to be involved in muscle homeostasis and to be controlled by the Dys-nNOS-HDAC2 pathway. Exon skipping has been demonstrated to be a successful strategy for the gene therapy of Duchenne muscular dystrophy (DMD): the rational being to convert severe Duchenne forms into milder Becker ones. Here, we show the selection of U1 snRNA-antisense constructs able to confer effective rescue of dystrophin synthesis in a Δ44 Duchenne genetic background, through skipping of exon 45; moreover, we demonstrate that the resulting dystrophin is able to recover timing of myogenic marker expression, to relocalize neuronal nitric oxide synthase (nNOS) and to rescue expression of miRNAs previously shown to be sensitive to the Dystrophin-nNOS-HDAC2 pathway. Becker mutations display different phenotypes, likely depending on whether the shorter protein is able to reconstitute the wide range of wild-type functions. Among them, efficient assembly of the dystrophin-associated protein complex (DAPC) and nNOS localization are important. Comparing different Becker deletions we demonstrate the correlation between the ability of the mutant dystrophin to relocalize nNOS and the expression levels of two miRNAs, miR-1 and miR29c, known to be involved in muscle homeostasis and to be controlled by the Dys-nNOS-HDAC2 pathway.
Molecular features of the hepatitis B virus nucleocapsid T-cell epitope 18-27: Interaction with HLA and T-cell receptor
Authors: A Bertoletti, S Southwood, R Chesnut, A Sette, M Falco, G B Ferrara, A Penna, C Boni, F Fiaccadori, C Ferrari
Journal: Hepatology (1997)

The strength of the cytotoxic T lymphocyte (CTL) response is believed to influence the final outcome of hepatitis B virus (HBV) infection. Among the different CTL epitopes so far identified, the sequence 18-27 of the HBV nucleocapsid antigen is widely recognized by CTL of HLA-A2-positive patients with acute self-limited HBV infection, and represents the main component of a peptide-based therapeutic vaccine aimed at stimulating the antiviral CTL response in patients with chronic hepatitis B. In the present study, we further analyzed the features of this important HBV region by the following: 1) defining the contribution of individual residues of the epitope to the interaction with the T-cell receptor (TCR) and with the HLA-A0201 molecule; 2) assessing the antigenicity of this viral region in the context of the different HLA-A2 subtypes; and 3) testing whether this sequence can stimulate not only HLA-class I but also HLA class II restricted T-cell responses. A clear hierarchy was observed in the ability of individual residues to act as TCR or HLA binding sites. Furthermore, the sequence HBc18-27 was able to be recognized by specific CTL when presented in the context of different HLA-A2 subtypes. Finally, this HBV region was also found to stimulate HLA class II restricted T-cell responses. These data further increase the potential coverage and efficacy of therapeutic vaccines based on the HBc18-27 sequence.
A1.30 High 11β-HSD1 activity is associated with progression to rheumatoid arthritis in patients with early inflammatory arthritis
Authors: Dominika E Nanus, Andrew D Filer, Lorraine Yeo, Dagmar Scheel-Toellner, Gareth L Lavery, Paul M Stewart, Christopher D Buckley, Mark S Cooper, Karim Raza
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Variation in endogenous glucocorticoid (GC) activity during inflammation has been linked to susceptibility to developing rheumatoid arthritis (RA). In RA patients, inflamed synovial tissue can generate active GCs through the expression of the 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1), which converts cortisone to cortisol. We examined whether the total body activity of 11β-HSD1 or its expression within synovium was associated with the risk of developing RA in patients with newly presenting joint inflammation. <h3>Materials and Methods</h3> Blood and urine were collected from 42 patients with inflammatory arthritis and a clinical symptom duration of less than 12 weeks; of these 17 developed RA and 25 resolved spontaneously. Total body 11β-HSD1 activity was determined by urinary gas chromatography/mass spectrometry and calculated as the tetrahydrocortisol + allotetrahydrocortisol/tetrahydrocortisone ((THF + alloTHF)/THE) ratio and the cortols/cortolones ratio. Urinary 11β-HSD2 activity was measured as the urinary free cortisol/ urinary free cortisone (UFF/UFE) ratio. Synovial tissue expression of 11β-HSD1 and 11β-HSD2 was assessed by qPCR. Inflammatory disease activity was assessed by ESR, CRP and DAS28. <h3>Results</h3> Total body 11β-HSD1 activity was significantly lower in patients with arthritis that subsequently resolved compared with patients whose arthritis developed into RA (<b>RA</b> 1.34 ± 0.013, <b>Resolving arthritis</b>, 0.96 ± 0.07, P = 0.012). Similar changes were seen in the cortols/cortolones ratio (<b>RA</b> 0.64 ± 0.05, <b>Resolving arthritis</b>, 0.43 ± 0.03, P = 0.0002). There was no significant difference in renal 11β-HSD2 activity between patients with resolving disease and those that developed RA. Despite the difference in total body 11β-HSD1 activity there was no significant difference between groups in synovial tissue 11β-HSD1 expression. There was no difference in ESR or DAS28 between patients with resolving arthritis or RA although the former had a significantly lower level of CRP (<b>RA, </b>49 ± 16.7 mg/dL,<b> Resolving arthritis </b>19 ± 5.7 mg/dL, P = 0.018). All values are represented as mean ± SEM. <h3>Conclusions</h3> These studies demonstrate that a high total body 11β-HSD1 activity during early arthritis is associated with a reduced probability of resolution. The excess 11β-HSD1 may have an articular and/or extra-articular origin. This work raises the possibility that targeting 11β-HSD1 activity in early arthritis could impact on the development of RA.
A substantial tax on sugar sweetened drinks could help reduce obesity
Authors: J. P. Block
Journal: BMJ (2013)

Governments should act now, and real world evidence will follow 

Public health researchers, advocates, and policy makers have increasingly proposed taxes on sugar sweetened drinks as a way to reverse the rising consumption of such drinks—a trend believed to be a major contributor to the global obesity epidemic. In a linked article (doi:10.1136/bmj.f6189), Briggs and colleagues have modelled the expected impact of such a tax on energy intake and the prevalence of obesity and overweight.1 

According to recent national data from the United States, 12-19 year olds consumed an average of 1260 kJ per day (301 calories) in sugar sweetened drinks.2 Adults over 20 years consumed 850 kJ per day.3 Consumption is lower in the United Kingdom—448 kJ per day for 4-18 year olds and 682 kJ per day for 19-64 year olds in one survey—but still substantial.4 In response, several European countries, including Hungary, Finland, and France, have recently levied or increased existing taxes on these drinks.5 In the United States, 34 states and the District of Columbia have food taxes that affect sugar sweetened drinks; 23 of these have taxes specifically targeting these drinks.6

The question remains—do these taxes …
Reliability of a new shoulder laxometer to assess inferior glenohumeral joint translation
Authors: M L Sein, R C Appleyard, J R Walton, T Bradley, G A Murrell
Journal: British Journal of Sports Medicine (2007)

Objective: This study tested the reliability of the ORI laxometer, a newly developed non-invasive device for testing inferior translation of the humeral head in humans. Design: The instrument was designed to measure displacement between the top of the acromion and the head of the humerus when loaded in a similar fashion to the sulcus sign. Participants and interventions: Sixteen healthy subjects (32 shoulders) were measured for inferior glenohumeral joint laxity. One observer used the laxometer in 16 subjects on three separate occasions for the intra-observer trial. Three observers measured the inferior shoulder laxity of six subjects on one occasion in the inter-observer trial. Asymptomatic and unstable shoulders were also compared in 12 subjects with shoulder instability. Main outcome measurements: Translation in the glenohumeral joint Results: The range of inferior translation of glenohumeral joint in these subjects was between 0.01 mm and 6.5 mm with a mean of 1.5 mm. The intraclass correlation coefficient (ICC) for inter-observer reliability was 0.74. For intra-observer reliability the ICC was 0.76. These results are considered to be good to excellent. There was no advantage gained by using data from all five cycles of testing compared with three cycles. In patients with shoulder instability, laxometer measurements were significantly greater in their unstable shoulders than in their normal shoulders. Conclusions: The laxometer is easy to use, painless and gives objective measures for inferior glenohumeral laxity, with good intra- and inter-observer reliabilities. The ORI laxometer may be useful for assessing and monitoring global glenohumeral joint laxity which usually involves inferior laxity.
Augmentation of Left Ventricular Contractility by Cardiac Sympathetic Neural Stimulation
Authors: Christian Meyer, Obaida R. Rana, Erol Saygili, Christopher Gemein, Michael Becker, Kay W. Nolte, Joachim Weis, Thomas Schimpf, Christian Knackstedt, Karl Mischke, Rainer Hoffmann, Malte Kelm, Dainius Pauza, Patrick Schauerte
Journal: Circulation (2010)

Electric stimulation of mediastinal sympathetic cardiac nerves increases cardiac contractility but is not selective for the left ventricle because it elicits sinus tachycardia and enhanced atrioventricular conduction. The aim of this study was to identify sympathetic neural structures inside the heart that selectively control left ventricular inotropy and can be accessed by transvenous catheter stimulation.In 20 sheep, high-frequency stimulation (200 Hz) during the myocardial refractory period with electrode catheters inside the coronary sinus evoked a systolic left ventricular pressure increase from 97+/-20 to 138+/-32 mm Hg (P<0.001) without changes in sinus rate or PR time. Likewise, the rate of systolic pressure development (1143+/-334 versus 1725+/-632 mm Hg/s; P=0.004) and rate of diastolic relaxation (531+/-128 versus 888+/-331 mm Hg/s; P=0.001) increased. The slope of the end-systolic pressure-volume relationship increased (2.3+/-0.8 versus 3.1+/-0.6 mm Hg/mL; P=0.04), as did cardiac output (3.5+/-0.8 versus 4.4+/-0.8 L/min; P<0.001). Systemic vascular resistance and right ventricular pressure remained unchanged. There was a sigmoid dose-response curve. Ultrasound analysis revealed an increase in circumferential and radial strain in all left ventricular segments that was significant for the posterior, lateral, and anterior segments. Pressure effects were maintained for at least 4 hours of continued high-frequency stimulation and abolished by beta1-receptor blockade. Histology showed distinct adrenergic nerve bundles at the high-frequency stimulation site.Cardiac nerve fibers that innervate the left ventricle are amenable to transvenous electric catheter stimulation. This may permit direct interference with and modulation of the sympathetic tone of the left ventricle.
Unsuspected Pulmonary Foreign Body
Authors: David S. Nightingale, James C. Thompson
Journal: New England Journal of Medicine (1963)

COUGH, hemoptysis and weight loss in a middle-aged man immediately raise a strong suspicion of pulmonary carcinoma, tuberculosis being the most important alternate diagnosis. Suppuration in parenchymal tissue distal to bronchi blocked by neoplasm is a common complication. Persistent parenchymal densities on films of the chest remain the most consistently accurate diagnostic tool for carcinoma of the lung,1 , 2 and the majority of patients subjected to curative resection for pulmonary carcinoma undergo thoracotomy on the basis of radiographic findings without tissue diagnosis.In the case presented below, the patient was operated upon with a presumptive diagnosis of carcinoma associated with pneumonitis. . . .