tbuckley/cabot-search huggingface dataset:
Difficult Medical Management
Authors: Andrew Zaager
Journal: JAMA (1991)

<i>Difficult Medical Management</i>was written as a companion to another WB Saunders Co product,<i>Difficult Diagnosis</i>, stressing therapeutics rather than patient evaluation. It is truly a multidisciplinary work by a diverse panel, including specialists in surgery, medicine, pediatrics, psychiatry, and their associated subspecialties. The book has 93 chapters, arranged alphabetically, each on a distinct diagnostic entity. The editor has avoided the temptation to rely overly on esoterica, a refreshing deviation that makes this textbook especially readable and particularly useful to practicing physicians. As an internist in private practice, I especially enjoyed the chapters on antimicrobial use during pregnancy and lactation, hypercholesterolemia, nosocomial pneumonias, and coronary disease in the surgical patient. The inclusion of such topics as snakebite, narcolepsy, Tourette's syndrome, and near drowning lends balance to the attention given to more commonplace illnesses. Each of the chapters is organized in roughly the same manner. Fundamental physiology and relevant epidemiologic data
The Induction of Vascular Endothelial Growth Factor by Ultrafine Carbon Black Contributes to the Increase of Alveolar-Capillary Permeability
Authors: Chih-Ching Chang, Hui-Fen Chiu, Yih-Shyuan Wu, Yi-Chih Li, Mei-Ling Tsai, Chen-Kuo Shen, Chun-Yuh Yang
Journal: Environmental Health Perspectives (2005)

Ultrafine carbon black (ufCB) can cause proinflammatory response and increase alveolar-capillary permeability. However, the mechanism underlying the increased permeability is not well characterized. Vascular endothelial growth factor (VEGF) is originally recognized as a vascular permeability factor. Oxidative stress generated by hydrogen peroxide (H2O2) stimulates VEGF gene expression. The purpose of this study was to explore the role of VEGF in ufCB-induced alveolar-capillary permeability. Intratracheal instillation of 200 μg ufCB in mice caused a significant and sustained increase of total proteins in bronchoalveolar lavage (BAL) fluid, with the maximal increase at 21 hr postinstillation. The influx of neutrophils did not significantly increase until 16 hr. It reached the highest level at 21 hr and returned to the basal level by 42 hr. Tumor necrosis factor-α was significantly elevated only at 4 hr. ufCB induced significant increases of VEGF in BAL fluid throughout the study period, with the peak increase at 16 hr. The nonsecreted isoform VEGF188 was not altered after 16 hr of exposure to ufCB. Moreover, there was a strong correlation between VEGF and total proteins in BAL fluid (R2 = 0.7352, p &lt; 0.01). In vivo study supported the role of reactive oxygen species (ROSs) in ufCB-induced VEGF release and protein leakage. The involvement of ROSs was strengthened by the fact that interventions with N-acetyl-cysteine prevented ufCB-induced generation of ROSs and VEGF in vitro. Our study for the first time demonstrates that ufCB induces the production of VEGF, which is associated with the increase of alveolar-capillary permeability. The induction of VEGF by ufCB acts through an ROS-dependent pathway.
A Tumor-Protective Role for Human Kallikrein-Related Peptidase 6 in Breast Cancer Mediated by Inhibition of Epithelial-to-Mesenchymal Transition
Authors: Georgios Pampalakis, Evangelia Prosnikli, Theodora Agalioti, Antonia Vlahou, Vassilis Zoumpourlis, Georgia Sotiropoulou
Journal: Cancer Research (2009)

Human kallikrein-related peptidase 6 (KLK6) was cloned as a putative class II tumor suppressor based on its inactivated expression in metastatic breast cancer. Here, we investigated the mechanism(s) underlying the silencing of KLK6 gene in metastatic breast cancer and its putative implications for tumor progression. We present evidence that tumor-specific loss of KLK6 expression is due to hypermethylation of specific CpGs located in the KLK6 proximal promoter. Methylation-dependent binding of methyl CpG-binding protein 2 and the formation of repressive chromatin mediated by localized histone deacetylation are critical components of KLK6 silencing in breast tumors. Re-expression of KLK6 in nonexpressing MDA-MB-231 breast tumor cells by stable cDNA transfection resulted in marked reversal of their malignant phenotype, manifested by lower proliferation rates and saturation density, marked inhibition of anchorage-independent growth, reduced cell motility, and their dramatically reduced ability to form tumors when implanted in severe combined immunodeficiency mice. Interestingly, inhibition of tumor growth was observed at physiologic concentrations of KLK6, but not when KLK6 was highly overexpressed, as observed in a subset of breast tumors. Differential proteomic profiling revealed that KLK6 re-expression results in significant down-regulation of vimentin which represents an established marker of epithelial-to-mesenchymal transition of tumor cells and in concomitant up-regulation of calreticulin and epithelial markers cytokeratin 8 and 19, indicating that KLK6 may play a protective role against tumor progression that is likely mediated by inhibition of epithelial-to-mesenchymal transition. We suggest that KLK6 is an epigenetically regulated tumor suppressor in human breast cancer and provide ways of pharmacologic modulation.
Chemical toxicity of red cells.
Authors: S Piomelli
Journal: Environmental Health Perspectives (1981)

Exposure to toxic chemicals may result in alterations of red cell function. In certain cases, the toxic effect requires a genetic predisposition and thus affects only a restricted number of individuals; in other instances, the toxic effect is exerted on the hematopoietic system of every person. Glucose-6-phosphate dehydrogenase deficiency is probably the most widespread genetic disorder. It is observed at highest frequency in populations from subtropical countries as a result of its selective advantage vis à vis falciparum malaria. The gene controlling this enzyme is located on the X-chromosome; thus, the defect is sex-linked. Individuals with a genetic defect of this enzyme are extremely susceptible to hemolysis, when exposed to oxidant drugs (such as certain antimalarials and sulfonamides) because of the inability of their red cells to regenerate NADPH. Lead poisoning result in profound effects on the process of heme synthesis. Among the steps most sensitive to lead toxicity are the enzyme delta-aminolevulinic acid dehydratase and the intramitochondrial step that leads to the incorporation of iron into protoporphyrin. By these mechanisms, in severe lead intoxication there is an accumulation of large amounts of delta-aminolevulinic acid (a compound with inherent neurotoxicity), and there are abnormalities of mitochondrial function in all cells of the body. Individuals living in an industrialized society are unavoidably exposed to some environmental lead. Recent evidence indicates that, even at levels of exposure which do not increase the blood lead level above values presently considered normal, abnormalities of heme synthesis are clearly detectable.
Females With Subclavian Vein Thrombosis May Have an Increased Risk of Hypercoagulability
Authors: Kendall Likes, Danielle Rochlin, Susanna M. Nazarian, Michael B. Streiff, Julie A. Freischlag
Journal: JAMA Surgery (2013)

<h3>Background</h3>Subclavian vein thrombosis (SVT) is usually caused by vigorous activity or extensive use of the upper extremity. Patients are tested for hypercoagulability if they present with a spontaneous clot unassociated with such activity. The objective of this study was to determine the prevalence of hypercoagulability in patients undergoing first rib resection and scalenectomy presenting with SVT.<h3>Methods</h3>Using a prospectively maintained database from August 2003 through June 2011, patients were retrospectively reviewed for hypercoagulability testing and clinical outcomes.<h3>Results</h3>One hundred forty-three patients (79 females and 64 males; mean [range] age, 32 [16-71] years) presented with SVT, of whom 55 patients (43 females and 12 males; mean age, 32 [16-61] years) had undergone hypercoagulable testing. Fourteen patients (25.5%) (12 females and 2 males; mean age, 27 [16-46] years) had an abnormal hypercoagulable profile. A factor V Leiden mutation was present in 6 patients, protein S deficiency in 4, a plasminogen-activator inhibitor-1 (PAI-1) deficiency in 2, and 1 patient each with protein C deficiency, anticardiolipin antibodies, factor VII mutation, factor II mutation, and antiphospholipid antibodies. Immediate and long-term postoperative vein patency was similar to patients without hypercoagulability. Patients were placed on lifelong anticoagulation therapy if they had a PAI-1, protein C, or protein S deficiency.<h3>Conclusions</h3>Patients with hypercoagulability do as well with first rib resection and scalenectomy for SVT as those without hypercoagulability. In our patient subset, more females were tested owing to a history of spontaneous thrombosis and an increased incidence of hypercoagulable disorders. Because of our findings, we believe younger women with SVT should undergo hypercoagulable testing to identify the need for long-term anticoagulation therapy.
THE RESULTS OF THE COMPLETE AND INCOMPLETE OCCLUSION OF THE ABDOMINAL AND THORACIC AORTAS BY METAL BANDS.
Authors: W. S. HALSTED
Journal: JAMA (1906)

<h3>[ABSTRACT.]</h3> [Dr. Halsted prefaced his remarks with a brief historical sketch of the results of ligation of the abdominal aorta in animals and man and demonstrated an instrument and the method employed in the application of the metal (aluminum) bands.] With the assistance of my house surgeon, Dr. W. M. F. Sowers, who most zealously aided me in making the experiments, and Dr. E. H. Richardson, a member of the surgical staff of the Johns Hopkins Hospital, during the past twelve months, I have been able to conduct experiments on the aortas of more than one hundred dogs and have noted particularly: 1.<i>The effects of occlusion</i>, partial and complete, immediate, mediate and ultimate on the blood pressure, general and local (above and below the band). The pressure below the band is lowered in proportion, roughly, to the amount of occlusion. The return of the pressure to approximately normal below
Antidepressants double suicidality in children, says FDA
Authors: Jeanne Lenzer
Journal: BMJ (2006)

Children and adolescents treated with antidepressants are nearly twice as likely to develop suicidality—suicidal thinking and behaviour—as similar children treated with placebo. This is the finding of a meta-analysis of 24 studies by the US Food and Drug Administration. The studies tested 4582 patients taking nine antidepressants versus placebo for major depressive disorder, obsessive-compulsive disorder, generalised anxiety disorder, attention deficit or hyperactivity disorder, and social anxiety disorder.

The FDA's analysis, published in this month's Archives of General Psychiatry is the final review of data that were previously analysed but not released by the FDA (2006;63:332-9). News of the secret data emerged in August 2004, and led to criticism of the FDA when it was learnt that Andrew …
Correction: Antacids Tabulation
Authors: LINDA K. MCCOY
Journal: Annals of Internal Medicine (1981)

Letters and Corrections1 September 1981Correction: Antacids TabulationLINDA K. MCCOY, PHARM.D.LINDA K. MCCOY, PHARM.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-95-3-394_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In reviewing "Neutralizing Capacity and Cost Effectiveness of Antacids" (1), I have discovered a few errors in the listings of Table 1 for the sodium content of the antacids. Of particular importance is the listing for Delcid (Merrell-National Laboratories, Cincinnati, Ohio), which should be 15 mg/5 mL and not 1.5 mg/5 mL. Other discrepancies are probably due to the manufacturers' reformulations of the products. According to the most recent product information, the following changes have occurred: Maalox TC (W. H. Rorer, Inc., Fort Washington, Pennsylvania), 0.8 mg/5 mL; Riopan Plus (Ayerst Laboratories, New York, New York), 0.3...Reference1. DRAKEHOLLANDER DD. Neutralizing capacity and cost effectiveness of antacids. Ann Intern Med. 1981;94:215-7. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Good Samaratin Hospital Phoenix, AZ 85062 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1981Volume 95, Issue 3Page: 394-394KeywordsSodium ePublished: 1 December 2008 Issue Published: 1 September 1981 PDF downloadLoading ...
Immunopathological studies on the cutaneous lesions in sarcoidosis
Authors: FRANCISCO P. QUISMORIO, OM P. SHARMA, STEBBINS CHANDOR
Journal: British Journal of Dermatology (1977)

We examined the immunohistology of the cutaneous granulomas in sarcoidosis. By direct immunofluorescence immunoglobulin deposits were found in the skin lesions of 5 to 8 patients. These consisted of IgM within blood vessel wall (5 patients), IgM at the epidermal-dermal junction (2 patients) and IgG within and around the granuloma (2 patients). A fibrin network was present within the granulomas. Biopsy of a Kveim test site but not of uninvolved skin or of an erythema nodosum lesion showed similar immunofluorescence findings. Sheep erythrocytes sensitized with IgG antibody adhered to epithelioid cells within the granuloma indicating the presence of surface Fc receptors. At the periphery of the granulomas were B-lymphocytes. These findings are similar to those described in nodal and pulmonary sarcoid granulomas, and suggest that humoral antibodies may be important in the pathogenesis of the sarcoid granuloma.
The Multiple Causes of Hypercalcemia in Malignant Disease
Authors: Louis M. Sherwood
Journal: New England Journal of Medicine (1980)

Almost 40 years have elapsed since Albright1 first suggested that the neoplastic tissue in a patient with renal-cell carcinoma and hypercalcemia might produce parathyroid hormone or a similar substance that would raise serum calcium. During this period, there has been enormous progress in our understanding of the fundamental biochemistry and physiology of para-thyroid hormone and vitamin D, and of the relation of these hormones to calcium homeostasis. In patients with elevated serum calcium and a known malignant disease, a variety of pathogenic mechanisms, both humoral and nonhumoral, have been proposed. The report by Stewart et al. in this issue of . . .
MALABSORPTION IN DEFICIENCY DISEASES
Authors: FRANCIS LOWELL BURNETT
Journal: JAMA (1927)

In discussing deficiency diseases, McCarrison<sup>1</sup>says: The term "deficiency diseases" is customarily applied to a group of maladies which are caused by the lack of one of the accessory food factors. This application, however, is too restricted and should embrace disorders also due to faulty and unbalanced food. The vitamins have been largely responsible for such a narrow outlook on the diseases which are either favored in their origin or initiated by an insufficient supply of these substances. By speaking of the antineuritic vitamin the attention is drawn to one system of the body, while others are ignored. But in experimental animals on a deficient diet without vitamin B there is loss of appetite, impaired digestion, diarrhea, colitis, unhealthy skin, low temperature, slow respiration, cardiovascular depression, progressive anemia and asthenia, long before nervous symptoms are produced. Do not these form a disease syndrome, in children especially, which is as
Exercise-induced ischemic arrhythmias in patients with previous myocardial infarction: Role of perfusion and tissue viability
Authors: Alberto Margonato, Alessandra Mailhac, Fabrizio Bonetti, Gabriele Vicedomini, Gabriel Fragasso, Claudio Landoni, Giovanni Lucignani, Claudio Rossetti, Ferruccio Fazio, Sergio L. Chierchia
Journal: Journal of the American College of Cardiology (1996)
THE RELATION OF HEART WEIGHT TO THE BASAL METABOLISM AS VARIED BY THYROID ADMINISTRATION
Authors: Francis M. Smith, Eaton M. MacKay
Journal: The Journal of Experimental Medicine (1932)

A linear relationship exists in the albino rat between the heart weight and the basal metabolic rate when varied by the administration of active thyroid material. It is suggested that this increase in heart weight which follows the increase in metabolism after thyroid is in the nature of a simple work hypertrophy of the myocardium.
Truncated apo B-70.5–containing lipoproteins bind to megalin but not the LDL receptor
Authors: Zhouji Chen, Jeffrey E. Saffitz, Mickey A. Latour, Gustav Schonfeld
Journal: Journal of Clinical Investigation (1999)

Apo B-100 of LDL can bind to both the LDL receptor and megalin, but the molecular interactions of apo B-100 with these 2 receptors are not completely understood. Naturally occurring mutant forms of apo B may be a source of valuable information on these interactions. Apo B-70.5 is uniquely useful because it contains the NH2-terminal portion of apo B-100, that includes only one of the two putative LDL receptor–binding sites (site A). The lipoprotein containing apo B-70.5 (Lp B-70.5) was purified from apo B-100/apo B-70.5 heterozygotes by sequential ultracentrifugation combined with immunoaffinity chromatography. Cell culture experiments, ligand blot analysis, and in vivo studies all consistently showed that Lp B-70.5 is not recognized by the LDL receptor. The kidney was identified as a major organ in catabolism of Lp B-70.5 in New Zealand white rabbits. Autoradiographic analysis revealed that renal proximal tubular cells selectively removed Lp B-70.5. On ligand blotting of renal cortical membranes, Lp B-70.5 bound only to megalin. The ability of megalin to mediate cellular endocytosis of Lp B-70.5 was confirmed using retinoic acid/dibutyryl cAMP–treated F9 cells. This study suggests that the putative LDL receptor–binding site A on apo B-100 might not by itself be a functional binding domain and that the apo B–binding sites recognized by the LDL receptor and by megalin may be different. Moreover, megalin may play an important role in renal catabolism of apo B truncations, including apo B-70.5.
Pheochromocytoma and Tricyclic Antidepressants
Authors: John S. Kaufmann
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Several cases of pheochromocytoma referred to this hospital were reviewed recently because of their atypical clinical courses. One such patient experienced a hypertensive episode accompanied by grand mal seizures subsequent to imipramine (Tofranil) administration. <h3>Report of a Case.—</h3> A 36-year-old patient was hospitalized during the 32nd week of her third pregnancy because of recurrent left occipital headaches. She had been followed up carefully and at no time had she manifested hypertension, tachycardia, diaphoresis, pallor, proteinuria, or urinary tract infection. Physical examination was normal, including a blood pressure of 125/75 mm Hg. She received meperidine (50 mg) and promethazine (50 mg) several times for relief of pain, and, because of a depressive reaction, she was given imipramine, 25 mg every eight hours, for four doses. Approximately six hours after the last dose of imipramine, she experienced three grand mal seizures over a two- to three-hour period. Blood pressures
Isolated Bibrachial Plexopathy in a Patient With Type 2 Diabetes
Authors: Suraj A. Muley, Gareth J. Parry, Nacide G. Ercan-Fang
Journal: Diabetes Care (2005)

Diabetic amyotrophy is typically a lumbosacral radiculoplexus neuropathy resulting in weakness, muscle wasting, and pain (1). Brachial plexus involvement has been occasionally described with lumbosacral radiculoplexus neuropathy (2–6), but isolated diabetic brachial plexopathy has been described only in a patient with diabetic ketoacidosis (7). We describe a patient with well-controlled type 2 diabetes who developed isolated bibrachial diabetic plexopathy.

A 56-year-old African-American man with a 13-year history of well-controlled diabetes (total glycohemoglobin 6.2%, normal 3.9–6.3%), on insulin for 5 years and having …
Crosstalk between Estrogen Receptor alpha 36, a Dominant Extra-Nuclear ER, and HER2 Promotes Tumor Cell Survival in Breast Cancer.
Authors: L. Jiang, J. Huang
Journal: Cancer Research (2009)

Abstract The ER-α36 protein is a 36kDa novel splice variant of the full length 66kDa ER-α. ER-α36 lacks both transcriptional activation domains of ER-α66 but retains the DNA-binding domain and partial dimerization and ligand-binding domains. It has been shown that ER-α36 could trigger membrane-initiated signaling in ER-α36 over-expressing 293 cells, suggesting that ER-α36 might have functions linked with activation of intracellular signaling.To further explore the mechanism(s) of ER-α36 activation of intracellular signaling, in particular the possible relationship between ER-α36 and HER2 in breast cancer, we performed a pilot study. First, we examined the correlation between ER-α36 and HER2 by immunohistochemistry (IHC) using a specific anti-ER-α36 antibody designed against a unique epitope located in the C-tail of ER-a36 which is not present in ER-α66. The results showed that the expression of ER-α36 was highly associated with HER2 in a cohort of 249 breast tumors (P&amp;lt;0.05). Then, we examined whether ER-α36 physically interacts with HER2 in breast cancer cell lines using co-immunoprecipitation (Co-IP) and Western blotting (WB) experiments. We found that ER-α36 interacts with HER2 in both MCF7/HER2 and BT474 cell lines. Second, we explored whether ER-α36 influences the activation of HER2 and its downstream signaling by knocking down ER-α36 expression in both MCF7/HER2 and BT474 cell lines. We found that knockdown of ER-α36 by siRNA abrogated the activation of P-HER2, as well as Akt and MAPK, in both MCF7/HER2 and BT474 cells. Finally, we asked the key question whether ER-α36 was associated with cell proliferation/survival. Strikingly, we found that when both MCF7/HER2 and BT474 cells were deprived of ER-α36 by siRNA, they died quickly, whereas control cells grew normally.In conclusion, our preliminary data suggests that there might be a crosstalk between ER-α36 and HER2 signaling, and that this crosstalk might promote tumor cell survival through HER2/Akt and/or HER2/MAPK signaling pathways in breast cancer. Thus, ER-α36 may be a valuable biomarker and a novel therapeutic target in breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2121.
Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients
Authors: Gilles Salles, Franck Morschhauser, Thierry Lamy, Noel Milpied, Catherine Thieblemont, Hervé Tilly, Gabi Bieska, Elina Asikanius, David Carlile, Joe Birkett, Pavel Pisa, Guillaume Cartron
Journal: Blood (2012)
Walking protects elderly people from dementia, studies show
Authors: Janice Hopkins Tanne
Journal: BMJ (2004)

Two American studies published in JAMA show that ordinary, frequent walking protects elderly men and women from dementia and cognitive decline.

One study, of men only ( JAMA 2004;292: 1447), was an offshoot of the Honolulu heart programme, which began following 8006 men of Japanese ancestry on the Hawaiian island of Oahu in 1965 to 1968 for development of cardiovascular disease. It was designed in a similar way to the Framingham study in Massachusetts.

The new study excluded men …
Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and -8 inhibition
Authors: Sai Mun Leong, Ban Xiong Tan, Baidah Bte Ahmad, Tie Yan, Lai Yuen Chee, Swee Tin Ang, Kian Ghee Tay, Liang Piu Koh, Allen Eng Juh Yeoh, Evelyn Siew-Chuan Koay, Yu-Keung Mok, Tit Meng Lim
Journal: Blood (2010)