tbuckley/cabot-search huggingface dataset:
Magnesium Sulfate in Digitalis Toxicity.
Authors: Robert H. Seller
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Magnesium Sulfate in Digitalis Toxicity.Robert H. Seller, M.D., F.A.C.P., Martin Neff, M.D., Saul Mendelssohn, M.D., Kwan E. Kim, M.D., (Associate), Charles Swartz, M.D., F.A.C.P.Robert H. Seller, M.D., F.A.C.P.Search for more papers by this author, Martin Neff, M.D.Search for more papers by this author, Saul Mendelssohn, M.D.Search for more papers by this author, Kwan E. Kim, M.D., (Associate)Search for more papers by this author, Charles Swartz, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-785_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThis study was undertaken to define the mechanism of the antiarrhythmic effect of magnesium sulfate in digitalis toxicity. We recently reported that hypomagnesemia facilitates the development of arrhythmias due to digitalis toxicity and these are terminated promptly by intravenous magnesium sulfate. Digitalis causes an egress of potassium from the myocardium. This myocardial potassium loss underlies the development of arrmythmias. In 16 dogs potassium and magnesium were measured in samples obtained simultaneously from the femoral artery and coronary sinus twice in a control period and at 2-min intervals after the administration of 1 mg acetylstrophanthidin into the right atrium. This was... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByThe role of magnesium in digitalis toxicity 1 May 1970Volume 72, Issue 5Page: 785-785KeywordsArrhythmiaCoronary arteriesFemoral arteriesHypomagnesemiaMagnesiumMyocardiumPotassiumSulfatesToxicity Issue Published: 1 May 1970 PDF DownloadLoading ...
Myocardial infarction and stroke associated with diuretic based two drug antihypertensive regimens: population based case-control study
Authors: I. Boger-Megiddo, S. R Heckbert, N. S Weiss, B. McKnight, C. D Furberg, K. L Wiggins, J. A C Delaney, D. S Siscovick, E. B Larson, R. N Lemaitre, N. L Smith, K. M Rice, N. L Glazer, B. M Psaty
Journal: BMJ (2010)

To examine the association of myocardial infarction and stroke incidence with several commonly used two drug antihypertensive treatment regimens. Design Population based case-control study. Setting Group Health Cooperative, Seattle, WA, USA.Cases (n=353) were aged 30-79 years, had pharmacologically treated hypertension, and were diagnosed with a first fatal or non-fatal myocardial infarction or stroke between 1989 and 2005. Controls (n=952) were a random sample of Group Health members who had pharmacologically treated hypertension. We excluded individuals with heart failure, evidence of coronary heart disease, diabetes, or chronic kidney disease. Exposures One of three common two drug combinations: diuretics plus beta blockers; diuretics plus calcium channel blockers; and diuretics plus angiotensin converting enzyme inhibitors or angiotensin receptor blockers.Myocardial infarction or stroke.Compared with users of diuretics plus beta blockers, users of diuretics plus calcium channel blockers had an increased risk of myocardial infarction (adjusted odds ratio (OR) 1.98, 95% confidence interval 1.37 to 2.87) but not of stroke (OR 1.02, 95% CI 0.63 to 1.64). The risks of myocardial infarction and stroke in users of diuretics plus angiotensin converting enzyme inhibitors or angiotensin receptor blockers were slightly but not significantly lower than in users of diuretics plus beta blockers (myocardial infarction: OR 0.76, 95% CI 0.52 to 1.11; stroke: OR 0.71, 95% CI 0.46 to 1.10).In patients with hypertension, diuretics plus calcium channel blockers were associated with a higher risk of myocardial infarction than other common two drug treatment regimens. A large trial of second line antihypertensive treatments in patients already on low dose diuretics is required to provide a solid basis for treatment recommendations.
Malabsorption of Folate Polyglutamates Associated with Oral Contraceptive Therapy
Authors: Thomas F. Necheles, L. Michael Snyder
Journal: New England Journal of Medicine (1970)

DRUG-induced malabsorption of the dietary form (folate polyglutamates) of folic acid has been recognized as a possible cause of megaloblastic anemia.1 , 2 The drug studied was diphenylhydantoin, but Streiff3 has suggested that oral contraceptive agents may have a similar effect. We wish to describe two women in whom folate-responsive megaloblastic anemia appeared after prolonged therapy with oral contraceptives. In both cases, as well as in four healthy women, therapy with contraceptive agents suppressed the rise in serum folate levels that usually follow ingestion of folate polyglutamates.Case 1. D.P., a 45-year-old woman, was well until 2 months before admission, when fatigue . . .
Upper-Gastrointestinal Tract Hemorrhage
Authors: Robert M. Zollinger
Journal: JAMA (1970)

Upper-gastrointestinal tract hemorrhage is a terrifying experience for the patient and an urgent challenge to the physician. Despite the best treatment and the widespread use of whole blood, patients with upper-gastrointestinal tract hemorrhage continue to have mortality of more than 10%.<sup>1-3</sup>The outlook is even more distressing in elderly patients and in those with associated diseases. Why are patients still bleeding to death? Has the ready availability of blood dulled our sense of urgency? Is there delay in initiating therapy, or is current therapy ineffective? Are we so absorbed in how well the patient responds to the initial therapy that the operative mode of treatment has not been selected until the patient is in more serious condition than when the treatment was started? Have we felt too capable of our own surgical skills and failed to vary the technical approach in these patients to meet the risks encountered? <h3>Bleeding</h3>
Pleurectomy in the management of massive pleural effusion associated with primary lymphoedema: demonstration of abnormal pleural lymphatics.
Authors: M Lewis, J Kallenbach, M Zaltzman, A Conlan, S Zwi, J Abramowitz
Journal: Thorax (1983)

Pleural effusions occur in patients with primary lymphoedema.Twenty such cases from published reports have been reviewed by Beer et al.'Although these effusions may be massive with rapid reaccumulation after thoracocentesis, we have been able to find only two brief reports of cases in which obliteration of the pleural space by pleurectomy2 3 was considered necessary.We have found no histological documentation of the abnormality of the pleural lymphatics in this condition.We report a case of primary lymphoedema with recurrent massive pleural effusions successfully treated by pleurectomy. Case reportA 46-year-old man first presented to the Johannesburg Hospital in 1978 with generalised primary lymphoedema associated with bilateral pleural effusions.The case was reported by Warman et al.4 Pulmonary function studies showed an appreciable restrictive defect and hypoxaemia (table).
Migration of gall stones.
Authors: T V Taylor, C P Armstrong
Journal: BMJ (1987)

The factors influencing the migration of gall stones are ill understood. Altogether 331 patients undergoing cholecystectomy were studied prospectively. The diameters of the cystic and common bile ducts and of stones in the gall bladder and bile ducts were measured. Increasing pressure was applied to the freshly excised gall bladder in an attempt to evacuate stones through the cystic duct. Stones passed in 33 (60.0%) of patients with choledocholithiasis, 45 (67.2%) of patients with pancreatitis, and 7 (3.2%) of patients without either pancreatitis or choledocholithiasis. Stones migrated in 6 (3.0%) who had a normal cystic duct diameter (less than or equal to 4 mm) and in 46 (32.5%) with a duct over 4 mm diameter. Common bile duct stones were often larger than the diameter of the cystic duct and when reintroduced into the gall bladder would not migrate. The passage of debris (less than or equal to 1 mm) through the cystic duct bore no relation to the presence or absence of choledocholithiasis or a dilated cystic duct. Small stones (1-4 mm diameter) must migrate to initiate and facilitate further migration; some must increase in size in the common bile duct. Increased biliary pressure consequently dilates the duct system retrogradely, allowing larger stones to follow. Patients at risk of stone migration and thereby pancreatitis and jaundice have large ducts that can be detected by ultrasound assessment.
High expression of lipoprotein lipase in poor risk B-cell chronic lymphocytic leukemia
Authors: D Heintel, D Kienle, M Shehata, A Kröber, E Kroemer, I Schwarzinger, D Mitteregger, T Le, A Gleiß, C Mannhalter, A Chott, J Schwarzmeier, C Fonatsch, A Gaiger, H Döhner, S Stilgenbauer, U Jäger
Journal: Leukemia (2005)
Abstract C15: Therapeutic benefit of targeting ERK in mutant KRAS in pancreatic ductal adenocarcinoma (PDAC)
Authors: Tikvah K. Hayes, Nicole F. Neel, Melissa Chenard, Jen Jen Yeh, Ahmed Samatar, Channing J. Der
Journal: Cancer Research (2013)

Abstract The limited success of anti-MEK and anti-RAF therapies with KRAS mutant cancers has been attributed, in part, to de novo or acquired resistance mechanisms that arise after prolonged treatment. A majority of resistance mechanisms involve kinome reprograming to reactivate ERK downstream of inhibitor activity. Therefore, we hypothesized that directly targeting ERK would be an effective method for overcoming these resistance mechanisms. To address this possibility, we evaluated the sensitivity of a panel of mutant KRAS pancreatic ductal adenocarcinoma (PDAC) cell lines to the highly selective SCH772984 ERK1/2 protein kinase inhibitor. First, we found that the anchorage-dependent growth of 6 of 12 cell lines were sensitive to SCH772984 treatment (IC50&amp;lt;2 μM). Some sensitive PDAC lines were resistant to the AZD6244 MEK1/2-selective inhibitor, indicating different mechanisms of action of these two inhibitors. Second, we identified phospho-AKT as a potential biomarker for PDAC SCH772984 sensitivity. Third, we assessed the molecular basis for anchorage-dependent growth inhibition. After 72 h treatment, flow cytometry analyses indicated impaired cell cycle progression through G1. Additionally, we found increased apoptosis as measured by formation of cleaved caspase-3. Together these observations suggest that sensitivity is a result of both impaired cell cycle progression and induction of apoptosis. Surprisingly prolonged SCH772984 treatment (2 weeks) resulted in senescence, as sensitive lines stained positive for senescence-associated beta-galactocidase. Furthermore, we found that senescent cells induced p16 and lost phospho-RB two common markers associated with induction of senescence. Onset of senescence was dependent on the loss of total MYC protein expression. Finally, we found that treatment with SCH772984 reduced tumorigenic growth in an in vivo xenograft mouse model. Our ongoing studies include determining the mechanisms of inhibitor resistance. In summary, our findings suggest that targeting ERK will be therapeutically beneficial for the treatment of KRAS mutant PDAC. Citation Format: Tikvah K. Hayes, Nicole F. Neel, Melissa Chenard, Jen Jen Yeh, Ahmed Samatar, Channing J. Der. Therapeutic benefit of targeting ERK in mutant KRAS in pancreatic ductal adenocarcinoma (PDAC). [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C15.
Radiotherapy of Bladder Tumors
Authors: William L. Caldwell
Journal: JAMA (1967)

<h3>To the Editor:—</h3> The conclusions of the recent preliminary communication, "Bladder Carcinoma: Combined Radiotherapy and Surgical Treatment," by DeWeerd and Colby (<b>199</b>:109, 1967) were that combined therapy is perhaps the logical initial treatment for cases of infiltrative bladder carcinoma. Certainly definitive treatment for invasive bladder tumor is often inordinately delayed, and the authors' recommendation for aggressive initial treatment is lauded. The possibilities of modern radiotherapy alone in the treatment of bladder cancer perhaps have been misrepresented in the presentation. One of the two recent references regarding radiotherapy quoted is a report by Sir Eric Riches, a urologist. The interested reader is referred to several pertinent publications<sup>1-7</sup>which report results of radiotherapy alone to be as good as those by radical surgery with or without preoperative radiotherapy. Comparison of results of treatment by irradiation with results of cystectomy is often hazardous, particularly if the operative series are staged according
Spotlight on preconditioning
Authors: D Yellon
Journal: Cardiovascular Research (2002)

The phenomenon of ischaemic preconditioning, in which a period of sublethal ischemia can profoundly protect the cell from subsequent lethal ischemic insult, has without doubt been responsible for an enormous amount of research over the last 15 years. Since the original publication in 1986 by Murry et al. [1] there have been in excess of 2000 publications directly attributed to this phenomenon. Furthermore it is virtually impossible to find a publication that fails to demonstrate the ability of sublethal ischemia to protect the myocardium from a lethal ischemic insult thus attesting to the power of the phenomenon of ischemic preconditioning. This early form of protection has become know as “classic or early preconditioning”. This was followed in 1993 by the first description of the “Second Window of Protection” or delayed preconditioning (sometimes referred to as late preconditioning) by Marber et al. [2] in which a second period of protection was observed 24 h after a sublethal ischemic insult. For those interested in statistics it may be noted that the original article in which this phenomenon was first described in 1986 is the most cited article that Circulation has ever published, with that describing the delayed or second window as the 15th most cited paper by that journal.

That a myocardial cell has an innate ability to protect itself from severe lethal ischemia based upon what it can “learn” from a prior sublethal ischemic insult has caught the imagination of basic and clinical scientists all over the world. What is believed to be so unique about this phenomenon is that it tells us how a cell tries to survive a severe ischemic insult. It is therefore important to try and understand the myriad of pathways that are associated with this survival mechanism. From the initial receptor that triggers or initiates the … 

* Corresponding author. Tel.: +44-207-380-0591; fax: +44-207-388-5095
The effects of dasatinib on IgE receptor–dependent activation and histamine release in human basophils
Authors: Michael Kneidinger, Uwe Schmidt, Uwe Rix, Karoline V. Gleixner, Anja Vales, Christian Baumgartner, Christian Lupinek, Margit Weghofer, Keiryn L. Bennett, Harald Herrmann, Alexandra Schebesta, Wayne R. Thomas, Susanne Vrtala, Rudolf Valenta, Francis Y. Lee, Wilfried Ellmeier, Giulio Superti-Furga, Peter Valent
Journal: Blood (2008)
Static and dynamic rigidities of normal and sickle erythrocytes. Major influence of cell hemoglobin concentration.
Authors: E Evans, N Mohandas, A Leung
Journal: Journal of Clinical Investigation (1984)

Static and dynamic deformabilities of erythrocytes are important determinants of microcirculatory blood flow. To determine the influence of increased cellular hemoglobin concentration on these properties, we quantitated static and dynamic deformabilities of isolated subpopulations of oxygenated normal and sickle erythrocytes with defined cell densities using micromechanical manipulations of individual cells. The rheological properties measured to characterize static deformability were membrane extensional rigidity and bending rigidity. To characterize dynamic deformability of the cells, we measured the time constants for rapid elastic recovery from extensional and bending deformations. The extensional rigidity of sickle cells increased with increasing cell hemoglobin concentration while that of normal cells was independent of the state of cell hydration. Moreover, sickle cells were found to exhibit inelastic behavior at much lower cell hemoglobin concentrations than normal cells. In contrast, the dynamic rigidity of both normal and sickle cells was increased to the same extent at elevated hemoglobin concentrations. Moreover, this increase in dynamic rigidity with increasing cellular dehydration was much more pronounced than that seen for static rigidity. Both the increased static and dynamic rigidities of the dehydrated sickle cells could be greatly improved by hydrating the cells. This suggests that increased bulk hemoglobin concentration, which is perhaps inordinately increased adjacent to the membrane, plays a major role in regulating the rigidity of sickle cells. In addition, irreversible membrane changes also appear to accompany cell dehydration in vivo, resulting in increased membrane shear rigidity and plastic flow. We expect that the marked increases in rigidity of dehydrated sickle cells observed here may have a major influence on the dynamics of their circulation in the microvasculature.
XIAP deficiency is a mendelian cause of late-onset IBD
Authors: Carsten Speckmann, Stephan Ehl
Journal: Gut (2013)

Sir,

We read with interest the review by Holm Uhlig on monogenic diseases associated with intestinal inflammation.1 XIAP deficiency, caused by X-linked inherited mutations in BIRC4 , is highlighted as a mendelian cause of very early onset IBD. Consistently with the observation of Crohn's disease (CD) in XIAP deficiency, the RING activity of XIAP was recently shown to be required for NOD2-dependent immune responses.2 In his review Dr Uhlig suggests to consider monogenetic diseases as causes for IBD particularly in patients younger than 6 years of age. In addition to the reviewed literature, our group has recently reported …
Antitrypsin Phenotypes in St. Louis
Authors: John A. Pierce
Journal: JAMA (1975)

Antitrypsin phenotypes were determined from 2,285 donors at the Barnes Hospital Blood Bank in St. Louis . Results resembled those obtained from Central Europeans: there were fewer proteinase inhibitor (Pi) Z alleles in St. Louis than in Scandinavian test groups. Interestingly, major antifrypsin variants occurred only 40% as frequently in black as in the balance of the study group.
Prevalence and clinical significance of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis
Authors: T Avcin, R Cimaz, F Falcini, F Zulian, G Martini, G Simonini, V Porenta-Besic, G Cecchini, M O Borghi, P L Meroni
Journal: Annals of the Rheumatic Diseases (2002)

<b>Background:</b> Antibodies against cyclic citrullinated peptide (anti-CCP) are considered to be specific for rheumatoid arthritis (RA). <b>Objective:</b> To assess the clinical significance of anti-CCP in a cohort of patients with juvenile idiopathic arthritis (JIA). <b>Methods:</b> Anti-CCP were tested by an enzyme linked immunosorbent assay (ELISA) in serum samples from 109 patients with JIA (30 boys, 79 girls), with a mean age of 8.7 years (range 0.6–20.3) and mean disease duration of 3.6 years (range 3 months to 15.6 years). As control groups, anti-CCP were also tested in sera of 30 healthy children, 25 patients with juvenile onset systemic lupus erythematosus (SLE), and 50 adult patients (30 with RA, 20 with SLE). <b>Results:</b> Positive anti-CCP values were found in sera of two patients with JIA (2%), one with polyarthritis, and one with oligoarthritis. Statistical analysis showed that anti-CCP were not associated with the presence of antinuclear antibodies, raised erythrocyte sedimentation rate, or erosions. In the control groups, none of the patients with juvenile onset SLE and only one of 20 adults with SLE were positive for anti-CCP, but 19/30 (63%) adults with RA showed anti-CCP positivity. <b>Conclusions:</b> Anti-CCP can be detected in children with JIA, but are less frequently present than in adults with RA.
Involvement of platelet-activating factor in cytokine production and neutrophil activation after hepatic ischemia-reperfusion
Authors: A Serizawa, S Nakamura, S Suzuki, S Baba, M Nakano
Journal: Hepatology (1996)

Although platelet-activating factor (PAF) is implicated as an important mediator in the pathogenesis of hepatic ischemia-reperfusion (IR) injury, the precise mechanism of its action has not been studied. We examined the hypothesis that PAF may influence neutrophils by promoting the production of tumor necrosis factor alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant (CINC), a member of the interleukin-8 (IL-8) family, and may be associated with liver and lung injury during the early phase of reperfusion after total hepatic ischemia. Rats pretreated with a specific PAF receptor antagonist exhibited suppression of the increase in plasma TNF-alpha and CINC levels, as well as the priming of peripheral neutrophils for superoxide production after reperfusion when compared with animals pretreated with physiological saline. These effects resulted in a reduction of plasma liver enzymes and of hepatic and pulmonary neutrophil sequestration, as well as an increased survival rate. There was a strong correlation between the time course of CINC release and hepatic or pulmonary neutrophil sequestration. We concluded that PAF activates neutrophils, either directly or by promoting the production of TNF-alpha and CINC, and is involved in hepatic IR injury.
Noninvasive determination of cardiac output in patients with severe airflow limitation.
Authors: L C Lands, G Canny, F Xu, A L Coates
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The noninvasive measurement of cardiac output (Q) by the Indirect Fick CO2-rebreathing technique requires mixed venous P CO2 (P CO2) to be determined by the rebreathing maneuver, and Pa CO2 to be estimated from end-tidal P CO2 (PET CO2). Previous work has suggested that although P CO2 can be determined, Pa CO2 cannot be accurately estimated in patients with significant airflow limitation. Nineteen patients with cystic fibrosis who had severe airflow limitation (%FEV1, 29.3 +/- 7.12 SD) were studied during steady-state exercise at 50% of their measured maximal work capacity. Estimated Pa CO2 was slightly lower than Pa CO2 measured from blood samples obtained from an indwelling arterial catheter (measured: 45.2 +/- 4.92; estimate: 42.7 +/- 5.68 mm Hg). To calculate arterial blood content, the values derived from Pa CO2, pH, hemoglobin (Hb), and O2 saturation were compared with those derived from PET CO2 and O2 saturation, where (1) pH was assumed to be 7.40 and Hb was measured, and (2) pH was assumed to be 7.40 and Hb was assumed to be 15 g/dl (measured mean pH, 7.34; Hb, 14.4 g/dl). No difference in arterial CO2 content was seen between the three methods (measured: 47.53 +/- 5.17; estimate 1: 49.57 +/- 6.58; estimate 2: 49.12 +/- 6.61 ml/100 ml). As pH and Hb can also affect mixed venous CO2 content, the effect on Q was also assessed. Both estimates fit closely with measured Q (r2=0.77 and 0.76), with intercepts not different from zero and slopes not different from 1, and coefficients of variation of 13.5 and 14.6%. When viewed with regard to the confidence intervals for Q as a function of O2 consumption, Q was altered to a minor extent. We conclude that the use of PET CO2 to estimate Pa CO2 can give reasonable values for Q determined noninvasively in patients with severe airflow limitation.