tbuckley/cabot-search huggingface dataset:
Pernicious Anemia— The Antithesis of Polycythemia
Authors: W. James Gardner
Journal: JAMA (1972)

<h3>To the Editor.—</h3> A recent letter, "Diphenylhydantoin in the Treatment of Duodenal Ulcer" (<b>219</b>:511, 1972), has encouraged me to express a long held hypothesis that both pernicious anemia and polycythemia are primarily of neurologic origin. In pernicious anemia the gastric mucosa is thin, pale, and atrophic. There is anacidity, low hemoglobin, posterolateral sclerosis, and no peptic ulcer. In polycythemia the gastric mucosa is thick, turgid, and hypertrophic. There is hyperacidity, elevated hemoglobin, no posterolateral sclerosis, and often peptic ulcer. All of which suggest that pernicious anemia may be the end result of sympathicotonia, ie, local sympathetic over-function (as in Raynaud's disease) affecting gastric mucosa. Conversely, its antithesis, polycythemia, may be the expression of the end result of vagotonia, ie, parasympathetic over-function affecting gastric mucosa. If this thesis is correct, both are primary neurologic disorders. Since splanchnicectomy raises gastric acidity and vagotomy lowers it, pernicious anemia should respond to the
Lactic Acidosis in Pheochromocytoma
Authors: ROBERT G. HOLLANDER
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 August 1987Lactic Acidosis in PheochromocytomaROBERT G. HOLLANDER, M.D.ROBERT G. HOLLANDER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-107-2-259 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Bornemann and associates (1) have stated that lactic acidosis may be the initial presentation of a pheochromocytoma. In addition to the patient they report, they also review three cases of pheochromocytoma presenting with lactic acidosis and one case of lactic acidosis occurring after epinephrine poisoning. They hypothesize that catecholamine excess may have induced lactic acidosis by virtue of its effect on intermediary metabolism and the peripheral vasculature. After review of the cases cited in their paper, I do not think that catecholamine excess was the cause of their lactic acidosis.Patient 5 (the reference case), and...References1. BORNEMANNHILLKIDD MSG. Lactic acidosis in pheochromocytoma. Ann Intern Med. 1986;105:880-2. LinkGoogle Scholar2. FULOPHOROWITZABERMANJAFFE MMAE. Lactic acidosis in pulmonary edema due to left ventricular failure. Ann Intern Med. 1973;79:180-6. LinkGoogle Scholar3. VAN VLIETBURCHELLTITUS PHJ. Focal myocarditis associated with pheochromocytoma. N Engl J Med. 1966;274:1102-8. CrossrefMedlineGoogle Scholar4. VELASQUEZD'SOUZAHACKSHAWGLASSFORMANEK GVBTA. Phaeochromocytoma and cardiomyopathy. Br J Radiol. 1984;57:89-92. CrossrefMedlineGoogle Scholar5. KOLENDORFMOLLER KB. Lactic acidosis in epinephrine poisoning. Acta Med Scand. 1974;196:465-6. CrossrefMedlineGoogle Scholar1. A 42-year-old woman with hypertension, hematemesis, and metabolic acidosis. N Engl J Med. 1985;312:568-75. CrossrefMedlineGoogle Scholar2. A 34-year-old man with hypertension and episodes of flushing, nausea, and vomiting. N Engl J Med. 1986;314:431-9. CrossrefMedlineGoogle Scholar3. COLICE G. Neurogenic pulmonary edema. Clin Chest Med. 1985;6:473-89. CrossrefMedlineGoogle Scholar4. REYNOLDS J ed. Martindale: The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press; 1982:6. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byType B lactic acidosis and metastatic breast cancer 1 August 1987Volume 107, Issue 2Page: 259-260KeywordsCatecholaminesEpinephrineLactic acidosisPheochromocytoma Issue Published: 1 August 1987 PDF downloadLoading ...
Consequentialism and Outrageous Options: Response to Commentary on “Consequentialism and Harsh Interrogations”
Authors: Matthew K. Wynia, American Medical Association*
Journal: The American Journal of Bioethics (2006)

*Disclaimer: The views expressed are the author's and should not be ascribed to the American Medical Association. Notes *Disclaimer: The views expressed are the author's and should not be ascribed to the American Medical Association.
Peritoneal Dialysis with Fructose Dialysate
Authors: RASIB M. RAJA
Journal: Annals of Internal Medicine (1973)

The effects of a 7% fructose solution were compared with those of a 7% dextrose solution, both with 120 meq/litre sodium, during four consecutive exchanges in 14 patients. The increase in blood total reducing substance and serum osmolality was significantly less marked with fructose than dextrose solution. There was no increase in serum sodium concentration. Three diabetic patients tolerated 48-hour peritoneal dialysis with a 1.5% fructose solution containing 140 meq/litre sodium. Blood total reducing substances did not exceed 250 mg/100 ml. There was no increase in blood uric acid concentration or decrease in venous blood pH. The peritoneal absorption of fructose was similar to that of glucose. A fructose dialysis solution may be indicated for diabetic patients and those who develop a hyperglycemic and hyperosmotic condition with dextrose solutions.
Sulindac and Renal Impairment
Authors: A. Whelton, W. Bender, F. Vaghaiwalla, M. Hall-Craggs, K. Solez
Journal: JAMA (1983)

<h3>To the Editor.—</h3> We noted the article by Drs Bunning and Barth, which suggests that sulindac may be used with safety in patients who have previously manifested evidence of renal impairment while receiving other nonsteroidal anti-inflammatory drugs (NSAIDs) (1982;248:2864). We agree with their statement that this clinical recommendation should be viewed as preliminary, especially in view of the short duration of sulindac therapy used in their patients and the increase in serum creatinine clearance and decrease in creatinine clearance noted during sulindac therapy in the third of their three patients. It is of unquestionable pathophysiological interest that, unlike other NSAIDs, sulindac does not decrease urinary prostaglandin excretion. However, a recent patient of ours who was initially seen with sulindacinduced renal failure, interstitial nephritis, and nephrotic syndrome had a clinical course and predisposing risk factors (severe congestive heart failure) similar to those in the nephrotoxic reactions reported with the other NSAIDs.
Self-Measurements for Asthma
Authors: Constantine J. Falliers
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Julius et al (229:663, 1974) have documented well the value of self-determined blood pressure readings in the management of "labile" hypertension. Their article, which emphasizes again the patient as<i>partner</i>, prompts me to recapitulate observations on the use of daily peak expiratory flow (PEF) measurements, taken by the patient at home or at work, for the investigation and the control of variable ("labile") obstructive lung disease. The instrument in common use is the Wright peak expiratory flow meter, a small, portable, and relatively simple apparatus, which almost anybody above the age of 4 or 5 years can learn to use reliably. Self-determinations of PEF by the patient two to four times daily, under diverse conditions of exposure, activity, and medication, provide a meaningful record of intermittent obstruction of the airways (<i>Ann Allergy</i>30:443, 1972). More sophisticated techniques, such as spirometry, plethysmography, and gas dilution studies, performed only
Cellular immune responses to ovalbumin and house dust mite in egg‐allergic children
Authors: T.‐W. Ng, P. G. Holt, S. L. Prescott
Journal: Allergy (2002)

Background: Although IgE‐mediated food (egg) allergy is typically lost with age the underlying immune mechanisms are not understood, particularly in relation to the development of persistent IgE‐mediated aeroallergen sensitivity. Methods: Lymphoproliferation and cytokine responses (IL‐5, IL‐10, IL‐13 and IFN‐γ) to house dust mite (HDM) allergen and egg ovalbumin (OVA) were assessed using peripheral blood mononuclear cells (PBMC) from children aged 6 months to 5 years ( n = 59) with acute IgE‐mediated egg allergy (urticaria and angiedema or anaphylaxis), as confirmed by positive skin prick testing (SPT). Of these 46 had positive SPT on the day of blood collection and 13 had outgrown egg allergy (negative SPT and successful egg challenge). Where possible, responses were compared with previous data from nonallergic children of similar ages ( n = 107). Results: Transient lymphoproliferative responses to OVA were seen in both egg‐allergic and nonallergic children, but were more marked and more prolonged in egg‐allergic children. Younger egg‐allergic children (&lt; 18 months) showed a mixed Th0 cytokine response to OVA, with readily detectable IFN‐γ, IL‐5, IL‐13 IL‐10. Although IL‐13 and IL‐5 responses (OVA) correlated in younger egg‐allergic children, there was a dissociation of these Th2 responses with age. Loss of clinical reactivity to egg was associated with almost complete loss of IL‐5 responses and OVA‐specific lymphoproliferation. Although IL‐13 levels tended to be lower with age, this was not significant. Strong IFN‐γ and IL‐10 responses to OVA persisted in older children after loss of OVA‐specific lymphoproliferation. Lymphoproliferative responses to HDM also developed earlier in egg‐allergic children compared with nonallergic children. Th1 (IFN‐γ) responses to HDM were largely below detection prior to 18 months of age, but increased significantly with age. In egg‐allergic children Th2 (IL‐5, IL‐13) HDM responses also progressively increased with age. At 3 years of age almost all egg‐allergic children had positive SPT to HDM and positive lymphoproliferative responses to HDM, with strong Th1 and Th2 (Th0) cytokine production. Conclusions: IL‐5 responses (rather than IL‐13) responses most closely reflected clinical food allergy, with dissociation of IL‐5 and IL‐13 responses in older and egg‐tolerant children. In this population, food and aeroallergen sensitivity was not associated with inability to produce IFN‐γ, but rather with mixed Th2 and Th1 (Th0) responses. Strong IL‐10 and IFN‐γ responses where associated with the development of tolerance, suggesting persistent ‘regulatory’ populations of OVA‐specific T cells, rather than clonal deletion of OVA responsive T‐cells.
Function of Cardiac Receptors
Authors: R. J. LINDEN
Journal: Circulation (1973)

Stimulation of right and left atrial receptors causes an increase in activity in sympathetic nerves [see table in the PDF file] to the sinoatrial node resulting in 1) an increase in heart rate, 2) a decrease in activity in nerves to the kidney, with an unknown effect, and 3) a diuresis caused by a blood-borne agent which is said by others to be a reduction in the concentration of antidiuretic hormone. This exciting finding leaves us with many questions both pure and applied. One may be important to us now. Remembering that these receptors have been vividly demonstrated in the atria of man should we not ask, Are these two small chambers not more important in man than commonly appreciated?
The Puerperium as a Factor in the Etiology of Multiple Neuritis and Degenerations of Nerve Tissue
Authors: H. Handford
Journal: BMJ (1891)

place one electrode over the sacrum and the other in the groini, and apply the secondary faradic current very weak to begin with, and gradually increase its strength as much as the patient can bear.In other cases one electrode may be placed in the vagina and the other in the groin.In another set botlh poles may be placed in the vagina, using the bipolar vaginal electrode.It is only by testing each case that it is possible to say whiich mode of administration will give the most relief.The effects derived from the secondary faradic current in these cases, anid used as we have described, are as follows:- 1.A marked dimlinution in the sensitiveness of the parts in
Multidrug Resistance Protein-1 Affects Oxidative Stress, Endothelial Dysfunction, and Atherogenesis via Leukotriene C <sub>4</sub> Export
Authors: Cornelius F.H. Mueller, Kerstin Wassmann, Julian D. Widder, Sven Wassmann, Chia Hui Chen, Barbara Keuler, Alexey Kudin, Wolfram S. Kunz, Georg Nickenig
Journal: Circulation (2008)

We recently showed that the multidrug resistance related protein-1 (MRP1) is important for the management of oxidative stress in vascular cells. However, the underlying mechanism and the in vivo relevance of these findings remain elusive. We hypothesize that inside-outside transport of leukotriene C(4) (LTC(4)) via MRP1 is a substantial proatherogenic mechanism in the vasculature. To test this hypothesis, we investigated the effects of MRP1 inhibition and LTC(4) receptor blockade (Cys-LT1 receptor) in vitro and in vivo.MRP1 is expressed abundantly in vascular smooth muscle cells (VSMCs). Pharmacological inhibition of MRP1 via MK571 reduces angiotensin II-induced reactive oxygen species release by 59% (L012 fluorescence) in VSMCs. The release of reactive oxygen species after angiotensin II stimulation also is inhibited by blockade of the Cys-LT1 receptor with montelukast. Incubation of VSMCs with recombined LTC(4) causes enhanced rates of reactive oxygen species and proliferation in wild-type and MRP1(-/-) VSMCs. Accordingly, the LTC(4) release in the cell culture supernatant of MRP1(-/-) VSMCs is significantly decreased compared with wild-type cells. To extend our observations to the in vivo situation, atherosclerosis-prone apolipoprotein E-deficient mice on a high-cholesterol diet were treated with placebo, the MRP1 inhibitor MK571, or the Cys-LT1 receptor inhibitor montelukast for 6 weeks. Treatment with MK571 or montelukast reduced vascular reactive oxygen species production, significantly improved endothelial function, and ameliorated atherosclerotic plaque generation by 52% and 61%, respectively.These findings indicate that MRP1 and LTC(4) exert proatherosclerotic effects and that both MRP1 and LTC(4) are potentially promising targets for atheroprotective therapy.
Chronic actinic dermatitis associated with human immunodeficiency virus infection
Authors: T. MEOLA, M. SANCHEZ, H.W. LIM, M.R. BUCHNESS, N.A. SOTER
Journal: British Journal of Dermatology (1997)

Chronic actinic dermatitis is a photodistributed, eczematous dermatitis that preferentially affects elderly men and persists for months to years. Its occurrence in individuals infected with human immunodeficiency virus (HIV) has been described in five patients. We report four additional cases of this uncommon, chronic photodermatosis associated with HIV infection. In two of the patients, photosensitivity was a presenting disorder leading to the diagnosis of HIV infection. All patients were men of skin type VI with a mean age of 50 years, all had decreased minimal erythema doses to ultraviolet B, three of the four patients had decreased minimal erythema doses to ultraviolet A and all had CD4 cell counts of < 200 x 10(6)/L.
Single-Agent Pemetrexed for Chemonaïve and Pretreated Patients with Malignant Pleural Mesothelioma: Results of an International Expanded Access Program
Authors: Paul Taylor, Bruno Castagneto, Graham Dark, Maurizio Marangolo, Giorgio V. Scagliotti, Rob J. van Klaveren, Roberto Labianca, Monika Serke, W Schuette, Jan P. van Meerbeeck, David Heigener, Yushan Liu, Susumu Adachi, Johannes Blatter, Joachim von Pawel
Journal: Journal of Thoracic Oncology (2008)
Basal and Postglucagon C-Peptide Levels in Ethiopians with Diabetes
Authors: Elias S Siraj, S. Sethu K Reddy, Werner A Scherbaum, Jemal Abdulkadir, Jeffrey P Hammel, Charles Faiman
Journal: Diabetes Care (2002)

To study basal C-peptide (BCP) and postglucagon C-peptide (PGCP) levels in Ethiopians with diabetes.A total of 56 subjects with type 1 diabetes, 97 subjects with type 2 diabetes, and 50 control subjects were recruited from a hospital in Ethiopia. BCP was determined in all subjects and PGCP in 86 subjects.Mean (+/- SEM) BCP, PGCP, and the increment after glucagon in type 1 diabetic subjects (0.14 +/- 0.04, 0.22 +/- 0.11, and 0.08 +/- 0.05 nmol/l, respectively) were lower (P < 0.001) than those in type 2 diabetic subjects (0.66 +/- 0.04, 1.25 +/- 0.10, and 0.56 +/- 0.06 nmol/l, respectively) or control subjects (0.54 +/- 0.04, 1.52 +/- 0.26, and 1.11 +/- 0.24 nmol/l, respectively). The mean BCP level was higher in type 2 diabetic subjects than control subjects (P=0.015), whereas the mean increment was lower (P=0.005). Insulin-treated type 2 diabetic subjects, compared with non-insulin-treated type 2 diabetic subjects, had lower mean BCP (0.55 +/- 0.08 nmol/l [n=37] vs. 0.73 +/- 0.04 [n=60], P=0.001), lower PGCP (0.97 +/- 0.20 nmol/l [n=18] vs. 1.40 +/- 0.11 [n=35], P=0.010), and a lower C-peptide increment (0.34 +/- 0.06 [n=18] vs. 0.67 +/- 0.07 nmol/l [n=35], P=0.003). In both the type 1 and type 2 diabetic groups, those with BCP levels <0.2 nmol/l had lower BMI than those with higher BCP levels (P=0.023 and P < 0.001, respectively).Combined with clinical criteria, C-peptide levels are good discriminators between type 1 and type 2 diabetes in Ethiopians and may also be useful in identifying subjects with type 2 diabetes who require insulin therapy. There is a subgroup of type 2 diabetic subjects with features of type 1 diabetes.
Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-γ production and the induction of Th1 cell differentiation
Authors: Naoki Tokumasa, Akira Suto, Shin-ichiro Kagami, Shunsuke Furuta, Koichi Hirose, Norihiko Watanabe, Yasushi Saito, Kazuya Shimoda, Itsuo Iwamoto, Hiroshi Nakajima
Journal: Blood (2007)
Abstract B08: Triptolide has antitumor effects in lung cancer via Wnt pathway inhibition.
Authors: Youqiang Li, Li Zheng, Binghui Shen, Jae Kim, Dan Raz
Journal: Clinical Cancer Research (2014)

Abstract Introduction: Triptolide is an extract of the herb Tripterygium wilfordii (Tw), which has been used to treat autoimmune disorders in traditional Chinese medicine. It has also been reported to have anti-cancer effects in vitro, although little is known about its mechanism of action. The Wnt/B-catenin pathway has been implicated in regulating cancer stem cells in lung cancer, making this pathway a potential target for novel lung cancer therapies. Methods: Here we tested the efficacy of triptolide in several lung cancer cell lines. We elucidated a Wnt pathway mechanism for triptolide effect in lung cancer, first by using a Wnt focused cDNA array in vitro. We examined the effect of triptolide on tumor cell death using flow cytomotery and a beta-galactosidase assay. We tested the ability of triptolide to prevent development of lung tumors in the E160D transgenic mouse model of lung cancer, which carries a somatic mutation in the DNA repair enzyme flap endonuclease-1 (FEN-1). Twelve month old mice were fed triptolide 1mg/kg daily for 2 months and were sacrificed at 18 months along with a control group. Results: Triptolide had more potent therapeutic efficacy in multiple lung cancer cell lines compared with cisplatin and paclitaxel, in vitro. In H460 and A549 cell lines, we found that triptolide resulted in Wnt pathway silencing via overexpression of Wnt inhibitory factor-1 (WIF-1), which occurs due to promoter demethylation. Addition of recombinant Wnt3a, which causes Wnt pathway activation, partially rescues the effect of triptolide on lung cancer cell lines. Triptolide resulted in cellular senescence as demonstrated by beta-galactosidase assay. Finally, in the E160D transgenic mouse model of lung cancer, a two month course of oral triptolide treatment decreased the development of lung tumors from 70% to 30% at 18 months (p=0.01). There were no observed clinical toxicities at the dosage of triptolide used. Conclusions: Triptolide has potent anti-cancer effects in vitro in lung cancer cell lines, and significantly decreases lung tumor development in a transgenic mouse model. Triptolide suppresses the Wnt pathway by causing upregulation of WIF-1a by promoter demethylation. Future studies are needed to test this promising and novel Wnt-targeting therapy in lung cancer animal models, and to identify biomarkers which may predict sensitivity in particular subgroups of lung cancer patients. Citation Format: Youqiang Li, Li Zheng, Binghui Shen, Jae Kim, Dan Raz. Triptolide has antitumor effects in lung cancer via Wnt pathway inhibition. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr B08.
APLASTIC ANEMIA DUE TO SULFATHIAZOLE
Authors: Leo M. Meyer
Journal: JAMA (1942)

The protean toxic manifestations of the sulfonamide group of drugs are generally well known and have recently been summarized by Long and Bliss<sup>1</sup>and Long, Haviland, Edwards and Bliss.<sup>2</sup>The hematologic changes have largely fallen into two main groups, namely agranulocytosis and hemolytic anemia.Leukemoid reactions are also mentioned. Thrombopenic purpura due to sulfathiazole has recently been observed.<sup>3</sup>The following case, showing the picture of aplastic anemia following the administration of sulfathiazole, represents the first to be reported in the literature, so far as we are aware. B. C., a housewife aged 55, an Assyrian, was admitted to the Long Island College Division of Kings County Hospital on Oct. 12, 1941 with a history of fever and malaise of two weeks' duration. One year previously the patient was told that she had "infected kidneys." At that time she had a mild febrile course. Two weeks before
Examining Methods to Assess Core Knowledge Competencies: A Canadian Perspective
Authors: Barbara Secker, Cécile Bensimon, Cheryl Cline, Dianne Godkin, Ann Heesters, Kevin Reel
Journal: The American Journal of Bioethics (2014)

Click to increase image sizeClick to decrease image size Notes The first author is the JCB Fellowship Director, the second author is the Fellowship Evaluation Coordinator, and the remaining authors are rotation supervisors and/or past fellows. See HEC Forum 24(3) for a special issue exploring the professionalization of practicing healthcare ethicists in Canada. The ASBH Core Competencies, 2nd edition (ASBH 2011), is one of the key reference documents informing the JCB Fellowship program, along with the Canadian Bioethics Society Taskforce on Working Conditions for Bioethics’ Model Role Description for Ethicists (Chidwick et al. Citation2010), which focuses on the ideal role and eight areas of responsibility of a PHE. The JCB Fellowship program is also informed by the emerging work of PHEEP (Practicing Healthcare Ethicists Exploring Professionalization), which anticipates the development of Canadian health care ethics practice standards (see Reel Citation2012). We are considering an expanded set of indicators as well a matrix summary approach to identifying incrementally demonstrated knowledge and skill acquisition. The matrix of required knowledge and skill competencies (see, e.g., Bingham et al. Citation2005) would be completed by fellows over the course of the fellowship, and domains/elements would be signed off by rotation supervisors and/or the fellowship director, attesting to the fellow having reached the thresholds expected in each domain. Such a matrix approach emphasizes formative assessment and allows for clear focus on those areas not yet achieved in order to ensure they are addressed within the year of the program. This approach has the advantage of being able to accommodate the variation in knowledge and skills among incoming JCB Fellows with typically interdisciplinary backgrounds.
Efficacy of imatinib mesylate in the treatment of idiopathic hypereosinophilic syndrome
Authors: Jorge Cortes, Patricia Ault, Charles Koller, Deborah Thomas, Alessandra Ferrajoli, William Wierda, Mary B. Rios, Laurie Letvak, Elizabeth S. Kaled, Hagop Kantarjian
Journal: Blood (2003)