tbuckley/cabot-search huggingface dataset:
Oral magnesium supplements reduce erythrocyte dehydration in patients with sickle cell disease.
Authors: L De Franceschi, D Bachir, F Galacteros, G Tchernia, T Cynober, S Alper, O Platt, Y Beuzard, C Brugnara
Journal: Journal of Clinical Investigation (1997)

Intracellular polymerization and sickling depend markedly on the cellular concentration of sickle hemoglobin (Hb S). A possible therapeutic strategy for sickle cell disease is based on reducing the cellular concentration of Hb S through prevention of erythrocyte dehydration. The K-Cl cotransporter is a major determinant of sickle cell dehydration and is inhibited by increasing erythrocyte Mg content. We studied 10 patients with sickle cell disease before treatment and after 2 and 4 wk of treatment with oral Mg supplements (0.6 meq/kg/d Mg pidolate). Hematological parameters, erythrocyte Na, K, and Mg content, erythrocyte density, membrane transport of Na and K, and osmotic gradient ektacytometry were measured. We found significant increases in sickle erythrocyte Mg and K content and reduction in the number of dense sickle erythrocytes. Erythrocyte K-Cl cotransport was reduced significantly. We also observed a significant reduction in the absolute reticulocyte count and in the number of immature reticulocytes. Ektacytometric analysis showed changes indicative of improved hydration of the erythrocytes. There were no laboratory or clinical signs of hypermagnesemia. Mild, transient diarrhea was the only reported side effect. We conclude that oral Mg supplementation reduces the number of dense erythrocytes and improves the erythrocyte membrane transport abnormalities of patients with sickle cell disease.
Biodegradation, biocompatibility, and drug delivery in poly(ω-pentadecalactone-co-p-dioxanone) copolyesters
Authors: Jie Liu, Zhaozhong Jiang, Shengmin Zhang, Chen Liu, Richard A. Gross, Themis R. Kyriakides, W. Mark Saltzman
Journal: Biomaterials (2011)
Nonenzymatically glycated albumin (Amadori adducts) enhances nitric oxide synthase activity and gene expression in endothelial cells
Authors: Alessandro Amore, Paola Cirina, Stefania Mitola, Licia Peruzzi, Bruno Gianoglio, Ivana Rabbone, Carla Sacchetti, Franco Cerutti, Caterina Grillo, Rosanna Coppo
Journal: Kidney International (1997)
Management of Infants with Cerebral Palsy
Authors: P. Robson
Journal: BMJ (1970)

are endemic could explain the finding of rickettsial antibodies in the sera of multiple sclerosis patients studied by Le Gac.It should be noted that rickettsiae are endemic not only in tropical Africa but also in northern Africa and other areas bordering the Mediterranean, including France.The only rickettsia affecting man known to be endemic in Britain is R. burneti, and no indication that Q fever is related to multiple sclerosis has been shown by the British in- vestigations involving microagglutination tests in altogether 79 and complement fixa- tion tests in 125 multiple sclerosis cases.I therefore agree with Professor Field and Miss Chambers and with my local colleagues that there is no acceptable evidence for a rickettsial aetiology of multiple sclerosis, and I see no grounds for diverting time and resources to clinical trial of Le Gac's treatment.-Iam, etc.,
The Cost of Marinol (Dronabinol)
Authors: Kirk V. Shepard
Journal: JAMA (1993)

<h3>To the Editor.</h3> —I would like to bring to your attention an error in the recent article entitled "The Lifetime Cost of Treating a Person With HIV" by Hellinger.<sup>1</sup> On page 478, in Table 4, "Drugs Approved After January 2,1992, to Treat Persons With the Human Immunodeficiency Virus (HIV)," the cost of Marinol (dronabinol) is listed as $183 per week and the dosage at 25 mg per day. Both the weekly cost and daily dosage as stated are incorrect. The correct dosage for treatment of anorexia associated with weight loss in patients with acquired immunodeficiency syndrome (AIDS) is one 2.5-mg Marinol capsule twice a day, before lunch and the evening meal. A bottle of 60 Marinol capsules, 2.5 mg each, has an average wholesale price to retail pharmacies of $179.40. Therefore, the average wholesale price to retail pharmacies for 1 week of therapy (14 capsules or 35 mg) is
The Metabolic and Respiratory Acidosis of Acute Pulmonary Edema
Authors: ARNOLD ABERMAN
Journal: Annals of Internal Medicine (1972)

Arterial blood gas tension and pH were measured in 50 consecutive patients with acute pulmonary edema due to left ventricular failure. In contrast to current belief that blood pH is typically normal or slightly alkaline in pulmonary edema, acidemia (pH below 7.36) was found in 38 of the 46 patients studied before treatment. Although patients with pulmonary edema are said to be characteristically hypocapnic, arterial CO2 tension was below 35 mm Hg in only half of these 46 patients. Eleven patients had arterial CO2 tension above 45 mm Hg, and 12 were eucapnic. The hypercapnic patients did not have more severe pulmonary edema or greater underlying chronic airway obstruction than those without CO2 retention. All but four patients survived the acute episode. The arterial CO2 tension and pH returned rapidly to normal, despite the routine cautious use of morphine, and with only the exceptional need for either ventilatory assistance or alkali administration.
BMA meeting: BMA urges no let up in fight against damaging changes
Authors: M. Limb
Journal: BMJ (2011)

The BMA’s chairman of council, Hamish Meldrum, warned the government this week that doctors would not let up in their opposition to damaging aspects of its reforms of healthcare in England.

Opening the BMA’s annual conference in Cardiff yesterday, he said that the BMA had already achieved major changes to the Health and Social Care Bill. These included revising the role of the economic regulator Monitor to promote integration rather than competition, restoring the health secretary’s responsibility for ensuring a comprehensive NHS, making commissioning more “inclusive,” and securing a more “realistic” timetable for reform.

But he told delegates that they must not …
Abstract 1071: Epidermal growth factor induces anterograde lysosome trafficking via activation of p38
Authors: Samantha S. Dykes, James A. Cardelli
Journal: Cancer Research (2012)

Abstract Previous studies from our laboratory have demonstrated that acidic extracellular pH and activation of c-Met by the Hepatocyte Growth Factor (HGF) in the tumor microenvironment, have the ability to induce anterograde (outward) lysosome trafficking in prostate tumor cells, resulting in an increase in protease secretion and tumor cell invasion. Lysosome redistribution requires microtubules, sodium proton exchangers (NHEs) and PI-3K activity. These processes can be blocked by preventing anterograde lysosome trafficking using NHE inhibitors or anti-diabetic drugs belonging to the thiazolidinedione class. Epidermal Growth Factor (EGF) is another growth factor that is commonly expressed in the tumor microenvironment, including prostate tumors, and is involved in activating a variety of processes leading to tumor progression. Upon binding of the EGF to Epidermal Growth Factor Receptor (EGFR), a variety of cellular survival and stress pathways are activated, ultimately resulting in cytoskeletal changes and altered gene expression that contribute to the increased motility and invasion of tumor cells. Interestingly, we have found that EGFR activation also induces anterograde lysosome trafficking and scattering in DU145 prostate cancer cells by a mechanism that is dissimilar to that of HGF-induced lysosome movement. For instance, we have determined that EGF anterograde lysosome trafficking and scattering is dependent on the activity of the mitogen activated protein kinase p38α, but is not dependent on the activity of PI3K. Conversely, HGF mediated lysosome trafficking and scattering is dependent on the activity of PI3K. Additionally, EGF induced peripheral lysosome movement appears to be independent of the activity of NHE 1 and 3, but treatment with the broad acting NHE inhibitor, EIPA [5-(N-ethyl-N-isopropyl)-amiloride], prevented EGF induced anterograde lysosome trafficking and promoted a clustering of lysosomes around the nucleus, suggesting that multiple NHEs are involved in EGF mediated lysosome trafficking. This was accompanied by a reduction in cell invasion through reconstituted basement membrane in a transwell invasion assay. Also, EGF-induced lysosome repositioning was reversed by troglitazone, an anti-diabetic agent. Together, these data further implicate lysosome positioning as critical to the process of HGF and EGF mediated tumor invasion and provide insight into the mechanism by which EGF induces peripheral lysosome trafficking. This information further supports the notion that inhibition of lysosome repositioning is a potentially viable therapeutic target to block HGF- and EGF-induced tumor cell invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1071. doi:1538-7445.AM2012-1071
Interactions Between Antibiotics and Oral Contraceptives
Authors: Rod J. True
Journal: JAMA (1982)

To the Editor.—  The response given in the QUESTIONS AND ANSWERS section to an inquiry concerning concurrent oral contraceptive (OC) and antibiotic therapy (1981;246:2076) warrants some comments. Dr Proudfit states that reported interactions of rifampin, ampicillin, and tetracycline with OCs presumably result because these drugs induce (I must assume the word include is a misprint in the reply, and the intended word is induce) hepatic microsomal enzymes.  While this is certainly important in the case of rifampin, ampicillin and tetracycline are not known to induce hepatic enzymes. Rather, the latter two drugs probably interact with OCs by another, unrelated mechanism. Synthetic estrogens undergo extensive enterohepatic recirculation, a process that probably involves the gut flora. The glucuronidated metabolites of the estrogens are secreted into the bile but cannot be reabsorbed from the intestine until the glucuronide moiety is hydrolyzed to regenerate free drug, a reaction that is carried out to a
Azelaic acid as a new treatment for perioral dermatitis: results from an open study
Authors: T. Jansen
Journal: British Journal of Dermatology (2004)

Sir, Until recently, the treatment of perioral (rosacea‐like) dermatitis has been considered to be difficult and frustrating.1 Many different substances have been employed, alone or in combination, locally or systemically. The choice has usually been occasioned by the physician's personal preferences, as the aetiology of the condition is still unknown. The mainstay of most treatment schemes has been oral tetracycline, which is effective in many cases but may be associated with adverse effects such as nausea, vomiting and phototoxicity. Topical treatments including antibiotics and metronidazole have been found useful but are not tolerated by many patients because of the unusually high skin sensitivity that often accompanies perioral dermatitis.2–4 The objective of this open clinical study was to investigate the efficacy and tolerability of a formulation containing 20% azelaic acid in 10 patients (nine women and one man; age range 32–65 years) with perioral dermatitis. At presentation, the condition had been present between 3 and 14 months. All patients had grouped erythematous papules, papulovesicles and/or papulopustules on a slightly scaling background with a distribution around the mouth, with a zone of sparing immediately adjacent to the lips. Telangiectases or comedones were not seen. There were no similar lesions on other parts of the face, especially in the periocular region. Six patients had previously used topical low‐ to high‐potency corticosteroids. Four patients had a history of atopy. All patients were negative when patch tested. Skin biopsy was performed in two patients, and showed a normal epidermis with a slight perivascular inflammatory infiltrate in the upper and mid dermis. The infiltrate consisted mainly of lymphocytes and histiocytes. No granuloma formation or Demodex mites could be demonstrated. The condition was not responsive to previous topical treatments, including antibiotics (five patients) and metronidazole (two patients). None of the patients had been given oral antibiotics.
Patient perspective: mild depression must not be ignored
Authors: S. Jessup
Journal: BMJ (2013)

<b>Introduction:</b> Prolonged mechanical ventilation in infants can result in ventilator associated lung injury. Premature extubation, however, can be associated with cardiorespiratory compromise. Identification of an accurate predictor of extubation success is, therefore, essential. <b>Aim:</b> To determine if diaphragmatic electrical activity during an SBT could predict extubation success in ventilated infants. <b>Methods:</b> Infants deemed ready for extubation by the clinical team were assessed. The SBT was performed when infants were on endotracheal CPAP for 5–10 minutes (mins). A failed SBT was recorded when the heart rate dropped &lt; 100bpm or a desaturation to 85% for &gt; 15 seconds, despite a 15% increase in FiO2. The diaphragmatic electrical activity was assessed using surface electrodes 10 mins pre, during and 10 mins post SBT. The clinical team were unaware of the SBT or the diaphragmatic EMG analysis results. Infants failed extubation if they were reintubated within 48 hours. <b>Results:</b> Twenty-eight infants, median (IQR) gestational age of 26.9 (25.2-28.4) weeks and post menstrual age&nbsp;(PMA)&nbsp;30.5 (27.9–35.4) weeks, were studied. During the SBT, the infants had increases in the mean EMG amplitude (3.6 versus 2.2 μV, p&lt;0.001) and mean area under the curve (MAUC) (5.3 versus 4 μV.s, p&lt;0.05). Seven infants failed extubation and had a greater&nbsp;percentage increase in the MAUC (40.4 versus 6.3 %, p&lt;0.05). A 29.6% increase in the MAUC during SBT had 71.4% sensitivity and 85.7% specificity in predicting extubation failure. <b>Conclusion:</b> The diaphragmatic EMG signal during SBT might have a role in predicting extubation failure in ventilated infants.
The unions are back in town
Authors: N. Timmins
Journal: BMJ (2010)

Health secretary Andy Burnham has been publicly uttering a phrase that we never heard from any of his five predecessors since Labour took office in 1997: “Our trade union colleagues.” And this is more than just rhetoric. NHS employers, the private and the voluntary sectors, and the health service trade unions all say the unions currently receive a hearing in Richmond House, the health department’s Whitehall headquarters, that they have not enjoyed for many years.

Not many people in the NHS may have heard of the Social Partnership Forum. It brings together the unions, NHS employers, and the department of health. Its nominal role is to discuss the workforce implications of policy. Since Mr Burnham took office, however, it has become a place where NHS policy is not merely debated but negotiated.

It wasn’t always thus. First set up in 1998 to encourage “partnership working” with NHS staff, it had by the mid-2000s, fallen in to desuetude.

“It wasn’t very strong to start with,” Michael Jackson, national officer for health with Unison remarks. In the early days, he says, “it existed. But it wasn’t taken very seriously.”

After the 2005 election, however, it fell apart—in large measure because, more or less out of the blue, Nigel Crisp, the then NHS chief executive, issued a notorious circular telling primary care trusts they had to get rid of their provider arms, outsourcing them to the private and voluntary sectors if need be.

“That severely damaged trust,” Mr Jackson says. The move caused such outcry among the quarter million staff employed by primary care trusts, among the unions, and among Labour MPs who had no idea that this was about to happen, that Patricia Hewitt, the then health secretary, had a torrid Labour party conference that autumn. She had to row back—rapidly and …
PHYSIOLOGIC OBSERVATIONS ON EXPERIMENTALLY PRODUCED ILEUS.
Authors: W. B. CANNON
Journal: JAMA (1907)

In his discussion of ileus, Nothnagel divides the condition into two classes: 1, Mechanical ileus, in which there is occlusion of the intestine; 2, dynamic ileus, in which there is a syndrome of occlusion of the bowel, without, however, closure of the lumen. The second class of cases occurs whenever the intestine becomes paralyzed, paretic or spastically stenosed.<sup>1</sup>Since an earlier paper in this discussion is concerned with intestinal obstruction, we shall not repeat here our observations, already published,<sup>2</sup>on certain physiologic changes following mechanical closure of the bowel. In that publication we raised the question as to the location of dynamic ileus. Is it of central or peripheral origin? In this research an attempt is made to answer that question. In dynamic ileus we are dealing directly with a failure of normal peristalsis. True peristalsis, according to Bayliss and Starling, is a coördinated movement dependent on this
THE DISCUSSION AT CAMBRIDGE ON THE FUTURE OF MEDICAL PRACTICE
Authors: P. Macdonald
Journal: BMJ (1920)

No more interesting or more valuable discussion has ever taken -place under the auspices of-any medical body than that held at the meeting.of the Section of Medical Sociology at the annual meeting of the British Medical Association at Cambridge on July 2nd.It ought to receive the closest attention of every medical practitioner, as it hinted at changes which may prove revolutionary, and will affect every member of the profession, whether general prac- titioner, consultant, laboratory workier, or State or muni cipal servant.The opener, Sir George Newman, was not very definite as regards proposals, except for his quite definite state- ment that he would do nothing to discourage that indi- vidualism which most medical .menwill agree is of peculiar value to medicine; but it was evident that both lie and those' who followed him''.werepleadina for
Three-Year Clinical and Angiographic Follow-Up After Intracoronary Radiation
Authors: Paul S. Teirstein, Vincent Massullo, Shirish Jani, Jeffrey J. Popma, Robert J. Russo, Richard A. Schatz, Erminia M. Guarneri, Stephen Steuterman, Kathleen Sirkin, David A. Cloutier, Martin B. Leon, Prabhakar Tripuraneni
Journal: Circulation (2000)

Background —Although several early trials indicate treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The objective of this report is to document angiographic and clinical outcome 3 years after treatment of restenotic stented coronary arteries with catheter-based 192 Ir. Methods and Results —A double-blind, randomized trial compared 192 Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192 Ir and 29 to placebo. At 3-year follow-up, target-lesion revascularization was significantly lower in the 192 Ir group (15.4% versus 48.3%; P &lt;0.01). The dichotomous restenosis rate at 3-year follow-up was also significantly lower in 192 Ir patients (33% versus 64%; P &lt;0.05). In a subgroup of patients with 3-year angiographic follow-up not subjected to target-lesion revascularization by the 6-month angiogram, the mean minimal luminal diameter between 6 months and 3 years decreased from 2.49±0.81 to 2.12±0.73 mm in 192 Ir patients but was unchanged in placebo patients. Conclusions —The early clinical benefits observed after treatment of coronary restenosis with 192 Ir appear durable at late follow-up. Angiographic restenosis continues to be significantly reduced in 192 Ir-treated patients, but a small amount of late loss was observed between the 6-month and 3-year follow-up time points. No events occurred in the 192 Ir group to suggest major untoward effects of vascular radiotherapy. At 3-year follow-up, vascular radiotherapy continues to be a promising new treatment for restenosis.
Quantitative x-ray microanalysis of the elemental composition of individual myocytes in hypoxic rabbit myocardium.
Authors: L M Buja, K P Burton, H K Hagler, J T Willerson
Journal: Circulation (1983)

The purpose of this study was to use energy dispersive x-ray microanalysis to test the following hypotheses: (1) that individual myocytes may exhibit important variation in the severity of alterations in intracellular ionic homeostasis in response to hypoxia and (2) that hypoxic myocytes may accumulate certain elements in quantities sufficient to impair organellar function and structure. A rabbit interventricular septal preparation with attached small right ventricular papillary muscles was used to obtain control oxygenated myocardium (six papillary muscles) and myocardium rendered hypoxic for 1 to 1 1/2 hr (n = 8). Myocardium not perfused in vitro was also obtained (n = 4). Microanalysis was performed on freeze-dried thin sections of unfixed papillary muscles. Elemental concentrations were determined by suitable cryostandards of elements of interest. Sarcoplasm and mitochondria of most hypoxic myocytes exhibited significant alterations of diffusible elements, including increases in sodium and chloride and decreases in potassium, phosphorus, and magnesium, without major change in calcium. The most severely altered myocytes showed evidence of calcium overloading manifested by markedly increased levels of mitochondrial calcium and phosphorus associated with formation of electron-dense mitochondrial inclusions. Levels of mitochondrial calcium and phosphorus exceeded those previously found to markedly impair the function and structure of isolated mitochondria. Thus x-ray microanalysis of unfixed cryosections provides direct measurements of subcellular alterations in elemental composition of individual myocytes in injured myocardium and demonstrates that both calcium and phosphorus accumulate in mitochondria of severely injured myocytes in concentrations sufficient to exert deleterious effects on these organelles.
Single-Institution, Multidisciplinary Experience with Surgical Resection of Primary Chest Wall Sarcomas
Authors: Puja Kachroo, Peter S. Pak, Harpavan S. Sandha, Catherine Lee, David Elashoff, Scott D. Nelson, Bartosz Chmielowski, Michael T. Selch, Robert B. Cameron, E. Carmack Holmes, Fritz C. Eilber, Jay M. Lee
Journal: Journal of Thoracic Oncology (2012)
Romania to change health system
Authors: T. Toma
Journal: BMJ (1997)

Romania is to switch from a centralised healthcare system to an insurance model similar to that of Germany, after a large majority in parliament endorsed the move this month.

From 1998 all employees will have to pay 5-7% of their total earnings in compulsory health insurance to a central company, Casa de Asigurari pentru Sanatate. The insurance company will then buy …
Nine drug company chiefs are charged with conspiracy to defraud NHS
Authors: Owen Dyer
Journal: BMJ (2006)

Nine British pharmaceutical executives have been charged with conspiracy to defraud the NHS, after an investigation by the Serious Fraud Office into price fixing of generic drugs.

Five companies have also been charged with colluding to keep prices high: Goldshield Group, Kent Pharmaceuticals, Norton Healthcare, Generics (UK), and Ranbaxy (UK). All the companies and individuals charged deny wrongdoing.

The Serious Fraud Office's inquiry, dubbed Operation Holbein, is one of its biggest ever cases, involving up to 150 investigators. Officers raided six companies in 2002. One, Regent-GM Laboratories, has since been wound up. The other five are those charged last week. …
Successful mobilization and engraftment of PBSCs derived from donor cord blood cells after a previous allogeneic RIC single unrelated cord blood transplantation
Authors: Fabrice Larosa, Eric Deconinck, Philippe Helias, Jean Fontan, Marian Heczko, Annie Brion, Katell Ledu, Philippe Delaby, Jacqueline Vuiller, Christophe Ferrand, Philippe Saas, Fabienne Pouthier, Anne Dormoy, Jacqueline Chabod, Caroline Malugani, Pierre S. Rohrlich, Faezeh Legrand
Journal: Blood (2011)