tbuckley/cabot-search huggingface dataset:
Defective Thyroglobulin Synthesis and Secretion Causing Goiter and Hypothyroidism *
Authors: GERALDO MEDEIROS-NETO, HECTOR M. TARGOVNIK, GILBERT VASSART
Journal: Endocrine Reviews (1993)

NORMAL growth and neurological development are dependent on a normal metabolic state, conditioned by an adequate supply of thyroid hormones. Synthesis of T3 and T4 follows a metabolic pathway that depends on the integrity of the thyroglobulin (Tg) structure. This large glycoprotein, a dimer of 660,000 daltons, is synthesized and secreted by the thyroid cells into the lumen of the thyroid follicle. Tg serves two main purposes in the function of the thyroid gland. The first is related to the process of hormone production. Thus Tg provides for the efficient coupling of the hormone precursors, mono- and diiodotyrosine to form T3 and T4. The second function is that of a repository within the gland of a large supply of iodine and of hormone for secretion at a steady rate or upon demand (1). These two properties of Tg seem to permit the organism to operate in an environment that is usually deficient in iodine and to adapt to wide variations in iodine supply. The efficiency of hormone synthesis in Tg depends on structural factors intrinsic to the protein matrix that favors the coupling reaction. We may assume that genetic mutations resulting in a structurally defective protein would severely impair the functional ability of Tg to serve as a matrix for T3 and T4 generation.
Piroxicam and Hyperkalemic Acidosis
Authors: LEONARD A. GROSSMAN
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 August 1983Piroxicam and Hyperkalemic AcidosisLEONARD A. GROSSMAN, M.D., SANDRA MOSS, M.D.LEONARD A. GROSSMAN, M.D.Search for more papers by this author, SANDRA MOSS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-99-2-282_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Several nonsteroidal antiinflammatory drugs have been associated with reversible azotemia and hyperkalemia (1). Piroxicam is a new, chemically unique, nonsteroidal antiinflammatory drug in the oxicam family (2). We have observed reversible, hyperkalemic, hyperchloremic acidosis associated with piroxicam therapy in a patient with rheumatoid arthritis.A 55-year-old man with a 25-year history of rheumatoid arthritis complicated by hypocomplementemic glomerulonephritis was hospitalized for bilateral total replacement of the hip. Therapy consisted of piroxicam, 20 mg/day, for 6 months, and chronic hypertension was controlled with propranolol, 40 to 60 mg/day. His previous arthritis treatment had included...References1. KIMBERLYBOWDENKEISERPLOTZ RRHP. Reduction of renal function by newer non-steroidal anti-inflammatory drugs. Am J Med. 1978;64:804-7. CrossrefMedlineGoogle Scholar2. WISEMAN E. Pharmacologic studies with a new class of non-steroidal anti-inflammatory agents—the oxicams—with special reference to piroxicam (Feldene (R). Am J Med. 1982;72:2-8. Google Scholar3. BLACKSHEARDAVIDSONSTILLMAN JMT. Identification of risk for renal insufficiency from non-steroidal anti-inflammatory drugs. Arch Intern Med. 1983;143:1130-4. CrossrefMedlineGoogle Scholar4. TANSHAPIROFRANCOSTOCKARDMULROW SRRHP. Indomethacin-induced prostaglandin inhibition with hyperkalemia: a reversible cause of hyporeninemic hypoaldosteronism. Ann Intern Med. 1979;90:783-5. LinkGoogle Scholar5. BRASSTHOMPSON EW. Drug-induced electrolyte abnormalities. Drugs. 1982;24:207-28. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: LEONARD A. GROSSMAN, M.D.; SANDRA MOSS, M.D.Affiliations: Rutgers Community Health Plan 57 U.S. Highway 1; New Brunswick, NJ 08901 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAdverse Reactions of PiroxicamOnce-daily oxaprozin and piroxicam compared in osteoarthritisAntiinflammatory and Immunosuppressive Drugs in the Treatment of Rheumatoid ArthritisSerum electrolyte abnormalities caused by drugsAntiinflammatory analgesics and durgs used in rheumatoid arthritis and gout 1 August 1983Volume 99, Issue 2Page: 282-282KeywordsArthritisDrugsGlomerulonephritisHypertensionRheumatoid arthritisTotal hip replacement ePublished: 1 December 2008 Issue Published: 1 August 1983 PDF downloadLoading ...
Evacuation decisions in chemical incidents benefit from expert health advice
Authors: Peter J Baxter
Journal: BMJ (2005)

exposure and the population.Evacuations generally entail moving people through a much higher exposure, albeit for a shorter duration.Our results show that direct exposure to smoke is a more important determinant of ill health than the cumulative exposure to smoke.These results are consistent with other studies. 3 7 Reasons for evacuation Despite the expert guidance, an unacceptably high proportion of chemical incidents worldwide result in evacuations.Possible reasons include an instinctive response on the behalf of emergency services to evacuate populations in danger, and the preference to "play it safe" by first responders, 3 and delay in getting appropriate advice.Initial decisions are often taken under very stressful conditions.Lack of experience has also been proposed since greater frequency of evacuations is reported from areas where chemical incidents are uncommon. 11 thank the participants in this study for taking the time to complete the questionnaires.We also appreciate the help provided by Geoff Chamings and Shaun Carter at Devon County Council, who converted the postcode references into distance between the factory and the residences.
Abstract 126: BRCA-positivity: Multicultural scenes from the rear view mirror .
Authors: Susan Miller-Samuel, Nicole Simone, Anne L. Rosenberg
Journal: Cancer Research (2013)

Abstract Background: To date, BRCA1 and BRCA2 mutations have been associated with specific breast cancer subtypes and patient demographics. BRCA testing has predominantly been performed in the Caucasian population. Certain breast cancer subtypes such as Triple Negative Breast Cancer (TNBC), have previously been associated with African American (AA) women and BRCA1 positivity. Novel targeted agents such as PARP inhibitors may be beneficial for TNBC and BRCA-positive cancers. Appropriate genetic referral and testing could influence patient treatment options. We sought to determine the patterns of patient referral and outcome for BRCA testing at Thomas Jefferson University Hospital (TJUH). Methods: After obtaining IRB approval, a retrospective case review was performed to identify women who proceeded with genetic counseling from January 2008 through May 2012. Patients with positive genetic tests were assessed. Pathology reports of mutation-positive women were reviewed. Patient characteristics such as ethnicity were confirmed from genetic counseling records. Findings: 461 new patients were seen for genetic counseling from January 2008 through May 2012. 309 (67%) proceeded with BRCA genetic testing and 26 (9%) were found to carry a deleterious BRCA1 or BRCA2 mutation. Hormone receptor profiles, age at diagnosis, and ethnic background varied among mutation carriers. The predominant ethnic background represented in TJUH mutation carriers is now AA. In 2008-2009 (24 months), only one AA woman was diagnosed with a BRCA mutation; however, from 2010-May 2012 (29 months), 9 AA women and 2 Hispanic women were diagnosed as BRCA-mutation carriers. Conclusions: BRCA-positive patients have diverse demographic and hormone receptor profiles. Although we found that TNBC remains associated with BRCA1 carriers and estrogen positivity with BRCA2 carriers, it is not absolute. A recent shift has noted substantially more AA women being diagnosed with BRCA mutations. While this may indicate that more diverse populations are being referred for genetic counseling, more importantly, it suggests that diverse populations are becoming more receptive to participating in genetic counseling and when appropriate, receiving genetic testing. Citation Format: Susan Miller-Samuel, Nicole Simone, Anne L. Rosenberg. BRCA-positivity: Multicultural scenes from the rear view mirror . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 126. doi:10.1158/1538-7445.AM2013-126 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
ENDOTHELIAL CELL ACTIVATION AND HIGH INTERLEUKIN-1 SECRETION IN THE PATHOGENESIS OF ACUTE KAWASAKI DISEASE
Authors: DonaldY.M. Leung, Evelyn Kurt-Jones, JaneW. Newburger, RamziS. Cotran, JaneC. Burns, JordanS. Pober
Journal: The Lancet (1989)
Evaluating general practitioner services
Authors: W. Weston-Davies
Journal: BMJ (1989)

ments made on a different occasion in awake children' and one study of adults in which no intra-arterial measurements were made.4We suggested using a maximum width cuff for convenience: it is easier to put the widest cuff possible on a child's arm than to refer to a chart based on measurements of the child's arm circumference.We accept that blood pressure is likely to vary with cuff size even with our criteria, but we believe that our technique is simple and that overestimation of blood pressure from too small a cuff is much more common than underestimation with a large cuff.We agree that cuff size should be varied as little as possible.
Glucose resistance contributes to diabetes mellitus in cirrhosis
Authors: Alexander S. Petrides, Dirk Schulze-Berge, Christoph Vogt, Dwight E. Matthews, Georg Strohmeye
Journal: Hepatology (1993)

Insulin resistance is a characteristic feature of glucose-intolerant and diabetic cirrhotic patients. The pathogenic factors, however, that are responsible for the development of impaired glucose tolerance in cirrhosis, remain unclear. To examine whether the ability of hyperglycemia per se to enhance glucose uptake (by means of mass-action effect) is impaired in cirrhosis, we measured (insulin-independent) whole-body glucose disposal during hyperglycemia (hyperglycemic clamp studies, +125 mg/dl, in combination with an infusion of somatostatin (500 micrograms/hr), insulin (0.1 mU/kg min) and glucagon (0.5 ng/kg min) to "clamp" hormone levels at baseline), whole-body glucose oxidation (indirect calorimetry) and glucose turnover (prime-continuous infusion of [6,6-2H2-]glucose in a clinically homogeneous group of cirrhotic patients with glucose intolerance (n = 7) or frank diabetes mellitus (n = 7) and in control individuals (n = 7). Fasting plasma glucose concentrations were normal in glucose-intolerant patients but were significantly increased in diabetic patients (158 +/- 19 vs. 87 +/- 2 mg/dl in controls; p < 0.01). Plasma glucose concentrations were clamped at 214 +/- 4 mg/dl in controls, at 212 +/- 4 mg/dl in glucose-intolerant patients and at 287 +/- 19 mg/dl in diabetic patients; plasma insulin and glucagon concentrations were maintained at baseline levels. In the basal state, total-body glucose disposal (which equals basal hepatic glucose output) was normal in glucose-intolerant patients (2.25 +/- 0.11 mg/kg min) but was increased in diabetic patients compared with controls (3.32 +/- 0.26 mg/dl vs. 2.45 +/- 0.10 mg/dl; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Bilamellar Cationic Liposomes Protect Adenovectors from Preexisting Humoral Immune Responses
Authors: Patricia Yotnda, Dong-Hua Chen, Wah Chiu, Pedro A Piedra, Alan Davis, Nancy Smyth Templeton, Malcolm K Brenner
Journal: Molecular Therapy (2002)

Adenoviral vectors have been widely used for gene therapy, but they are limited both by the presence of a humoral immune response that dramatically decreases the level of transduction after reinjection and by their requirement for target cells to express appropriate receptors such as Coxsackie adenovirus receptor (CAR). To overcome both limits, we encapsulated adenovectors using bilamellar DOTAP:chol liposomes. Electron micrography (EM) showed that these liposomes efficiently encapsulated the vectors, allowing CAR-independent adenovector transduction of otherwise resistant cells. DOTAP:chol-encapsulated adenovectors encoding LacZ or alpha(1)-antitrypsin inhibitor (AAT) were also functionally resistant ex vivo and in vivo to the neutralizing effects of human anti-adenoviral antibodies, unlike other liposomal systems. Hence, bilamellar DOTAP:chol liposomes may be useful for applications using adenovectors in which the target cells lack adenoviral receptors or in which the recipient already has or develops a neutralizing antibody response that would otherwise inactivate readministered vector.
Intracellular NAD levels regulate tumor necrosis factor protein synthesis in a sirtuin-dependent manner
Authors: Frédéric Van Gool, Mara Gallí, Cyril Gueydan, Véronique Kruys, Pierre-Paul Prevot, Antonio Bedalov, Raul Mostoslavsky, Frederick W Alt, Thibaut De Smedt, Oberdan Leo
Journal: Nature Medicine (2009)
Characterization of impurities in cefpodoxime proxetil using LC–MSn
Authors: Jin Li, Dousheng Zhang, Changqin Hu
Journal: Acta Pharmaceutica Sinica B (2014)

Reversed-phase liquid chromatography coupled with electrospray ionization tandem mass spectrometry (ESI-MS/MS) was used to characterize impurities in cefpodoxime proxetil, an ester-modified prodrug. Based on the mechanisms by which cephalosporins are degraded, stress tests were designed and performed. The bulk material and capsule were eluted through a C18 column with formic acid-methanol-water as the mobile phase. In total, 15 impurities were characterized in commercial samples, including 7 known impurities and 8 new impurities. The structures of these unknown compounds were deduced via comparison with the fragmentation patterns of cefpodoxime proxetil. Data from this systematic study will help improve the safety and quality of cefpodoxime proxetil.
Americans View Their Mental Health: A Nationwide Interview Survey
Authors: Janice Johnston
Journal: JAMA (1960)

What makes Americans happy or unhappy? What do they do when faced with problems and to whom do they turn? This book is a thoughtful and interesting effort to probe into these questions and is easy for the layman to understand. The survey concentrated first on those who experienced problems and the causes of these problems. It was found that the young and the educated experience the most problems and that this same group most often sought psychiatric help. Marriage, children, and "the job" proved to be the sources for the greatest problems. Economic status, not the world of the hydrogen bomb, was found to be the greatest single source of worry. The survey also asks how people resolve their problems once they are recognized. Many people pray; some go to clergymen, counselors, family doctors, or psychiatrists. The authors warn, however, that there is a growing shortage of trained psychiatric
Particulate Matter Oxidative Potential from Waste Transfer Station Activity
Authors: Krystal J. Godri, Sean T. Duggan, Gary W. Fuller, Tim Baker, David Green, Frank J. Kelly, Ian S. Mudway
Journal: Environmental Health Perspectives (2009)

BackgroundAdverse cardiorespiratory health is associated with exposure to ambient particulate matter (PM). The highest PM concentrations in London occur in proximity to waste transfer stations (WTS), sites that experience high numbers of dust-laden, heavy-duty diesel vehicles transporting industrial and household waste.ObjectiveOur goal was to quantify the contribution of WTS emissions to ambient PM mass concentrations and oxidative potential.MethodsPM with a diameter < 10 μm (PM10) samples were collected daily close to a WTS. PM10 mass concentrations measurements were source apportioned to estimate local versus background sources. PM oxidative potential was assessed using the extent of antioxidant depletion from a respiratory tract lining fluid model. Total trace metal and bioavailable iron concentrations were measured to determine their contribution to PM oxidative potential.ResultsElevated diurnal PM10 mass concentrations were observed on all days with WTS activity (Monday–Saturday). Variable PM oxidative potential, bioavailable iron, and total metal concentrations were observed on these days. The contribution of WTS emissions to PM at the sampling site, as predicted by microscale wind direction measurements, was correlated with ascorbate (r = 0.80; p = 0.030) and glutathione depletion (r = 0.76; p = 0.046). Increased PM oxidative potential was associated with aluminum, lead, and iron content.ConclusionsPM arising from WTS activity has elevated trace metal concentrations and, as a consequence, increased oxidative potential. PM released by WTS activity should be considered a potential health risk to the nearby residential community.
The Click-Murmur Syndrome and Anxiety Disorder-Reply
Authors: Melvin D. Cheitlin
Journal: JAMA (1981)

<h3>In Reply.—</h3> Dr Thase is quite correct in pointing out that chronic anxiety disorders have been commonly described in patients with CMS. Whether the underlying mechanism that causes the mitral valve apparatus prolapse also is responsible in some way for the psychological problems that the patients have or whether these common problems are unrelated is still not clear. There is intriguing evidence of elevated production of catecholamines or increased sympathetic nervous system activity or responsiveness, but so far this has not been unequivocally associated with the anxiety symptoms that the patients have.<sup>1,2</sup> Procacci et al,<sup>3</sup>in studying the entire female population of an air force base, identified all women with the auscultatory click, murmur, or both and found that the symptomatology of palpitations, dizziness, weakness, and chest pain were as common in the group without the auscultatory findings as those with the findings. Whether there is a causal
Deaths Involving Propoxyphene
Authors: William Q. Sturner
Journal: JAMA (1973)

Forty-one deaths occurred involving propoxyphene hydrochloride (Darvon) during a two-year period. Ten patients died from propoxyphene intoxication alone, while 12 were victims of a propoxyphene-alcohol combination, the latter number being identical to the deaths from a combination of barbiturates with alcohol seen during the same period. Five young women died from an ingestion of propoxyphene following an "argument." Four patients could be categorized as "drug abusers" due to historical circumstances. The high levels of propoxyphene suggested habituation in three instances. Physicians should be alerted to the potential deleterious effects of indiscriminate use and abuse of propoxyphene, and should warn their patients not to drink alcoholic beverages when taking propoxyphene. They should use extreme caution when prescribing it to those in the younger age group.
Low-Osmolar Contrast Agents-Reply
Authors: Peter D. Jacobson
Journal: JAMA (1989)

In Reply. —  We thank the authors of the above letters for their comments. In his letter, Dr Anthony raises a question about the percentage of patients who would be considered high risk as defined in our article. The estimate of 15% to 20% was based on our experience as well as estimates from several other hospitals. Certainly, this percentage will vary depending on the patient population and how rigidly the criteria are applied. We agree that additional data about the size of this high-risk group would be helpful.  We are in complete agreement with Dr Anthony's statement that physicians will be faced with more and more difficult decisions as we address the issues of placing limitations on the cost of medical care. We hope our case study of contrast agents will help physicians understand some of the complex medical, economic, legal, and public policy issues.  In their comments about
Lack of Benefit of Maintenance Paclitaxel in First-Line Chemotherapy in Metastatic Breast Cancer
Authors: Alessandra Gennari, Dino Amadori, Mario De Lena, Oriana Nanni, Paolo Bruzzi, Vito Lorusso, Luigi Manzione, Pier Franco Conte
Journal: Journal of Clinical Oncology (2006)

This randomized study compared maintenance paclitaxel with control in metastatic breast cancer patients not experiencing progression after first-line anthracycline/paclitaxel combination chemotherapy.Between April 1998 and October 2003, 459 metastatic breast cancer patients received first-line combination chemotherapy with epirubicin or doxorubicin plus paclitaxel. Of these, 255 who had a response or stable disease were then randomly assigned onto the Maintenance Paclitaxel 1 (MANTA1) study, comparing eight courses of maintenance paclitaxel versus control (ie, no additional chemotherapy administration). The primary end point was progression-free survival.The study was prematurely concluded after a futility analysis, which was performed on 215 of the 238 patients randomly assigned within December 2002. Of these, 109 patients were assigned to maintenance paclitaxel and 106 were assigned to stopping chemotherapy. No significant difference in median progression-free survival was observed (8.0 months for maintenance paclitaxel and 9.0 months for control). There was no significant difference in median survival time (28.0 v 29.0 months). When the Bayesian method for monitoring clinical trials was applied to these data, even under an enthusiastic prior distribution, in the posterior distribution there was only an 8.6% chance of observing a 3-month improvement in median progression-free survival in the group receiving maintenance paclitaxel. After these results study accrual was closed.Compared with control, the administration of additional courses of paclitaxel in patients who achieve disease control after six to eight courses of first-line anthracycline plus paclitaxel combination chemotherapy does not improve progression-free survival.