tbuckley/cabot-search huggingface dataset:
Malpractice — A Recent Case
Authors: Neil L. Chayet
Journal: New England Journal of Medicine (1965)

ON June 17, 1964, the largest malpractice award in history was handed down by the United States District Court in Pennsylvania.1 A judgment of $725,000 was rendered for Nathan Carl Schwartz, a forty-three-year-old attorney. The suit was brought against the United States because of the alleged negligence of Veterans Administration doctors.In 1944 a radioactive contrast dye (Umbrathor) was inserted into the plaintiff's sinus for x-ray purposes at the Naval Hospital at St. Albans, New York. After a medical discharge in 1945 Mr. Schwartz applied to the Veterans Administration Clinic, located in the Philadelphia Naval Hospital, complaining of continued sinus . . .
Leukotrienes and 8-isoprostane in exhaled breath condensate of children with stable and unstable asthma☆
Authors: Stefania Zanconato, Silvia Carraro, Massimo Corradi, Rossella Alinovi, Maria Francesca Pasquale, Giorgio Piacentini, Franco Zacchello, Eugenio Baraldi
Journal: Journal of Allergy and Clinical Immunology (2004)
Sinus Histiocytosis with Massive Lymphadenopathy
Authors: J. Dearth, D. Hunter, D. Kelly, W. Crist
Journal: CA A Cancer Journal for Clinicians (1980)

A 22-month-old child presented with massive cervical adenopathy accom panied by a retropharyngeal mass that caused stridoranddysphagia. Biopsy from both sides was consistent with sinus his tiocytosis with massive lymphadenopathy (SHML). SHML is an unusual benign lesion that characteristically presents with pain less, massive cervical adenopathy. Ex tranodal sites such as orbit, nose and skin are usually affected in association with cervical adenopathy. The pharyn geal involvement in this and several ot her recently reported cases adds to the het erogeneity of presentation of this un usual disease. The etiology remains un known. No treatment is required, nor is any treatment known to be consis tently effective. Gradual resolution of adenopathy over six months to several years is the expected outcome.
Narrative Review: Do State Laws Make It Easier to Say “I'm Sorry?”
Authors: William M. McDonnell
Journal: Annals of Internal Medicine (2008)

Initiatives intended to reduce the frequency and impact of medical errors generally rely on recognition and disclosure of medical errors. However, fear of malpractice liability is a barrier to physician disclosure. Some U.S. state legislatures have attempted to encourage physicians to disclose medical errors by enacting "apology laws." The authors reviewed the codified statutes of each of the 50 states and the District of Columbia to determine the prevalence and characteristics of such apology laws. They found that many states have recently adopted apology laws and that there is variability in these laws. The authors review some of the important differences in these laws and explore the potential impact of apology laws.
Abolishing Bax-Dependent Apoptosis Shows Beneficial Effects on Spinal Muscular Atrophy Model Mice
Authors: Ming S. Tsai, Yung T. Chiu, Sue H. Wang, Hsiu M. Hsieh-Li, Wei C. Lian, Hung Li
Journal: Molecular Therapy (2006)

Spinal muscular atrophy (SMA) is the most common genetic motoneuron degenerative disorder, but the mechanism(s) of motoneuron degeneration is unclear. We previously generated SMA model mice, which genotypically and phenotypically mimicked human SMA patients, by a combination of knockout and transgenic techniques. Here, we used these SMA model mice to decipher the apoptotic mechanism(s) involved in SMA motoneuron degeneration. We found a significant increase in proapoptotic Bax expression in the spinal cords of SMA mice in comparison with their wild-type littermates. After crossing SMA mice with Bax knockout mice, we produced in vivo evidence indicating that Bax protein plays an important role in the degeneration of SMA spinal motoneurons. Progeny Bax-deficient SMA mice showed milder disease severity, longer life spans, and significant increases in spinal motoneuron densities compared to SMA littermates with wild-type Bax genes. Our results strongly suggest that suppression of Bax-involved apoptosis has the potential for amelioration of SMA.
Effect of food consistency on gastric emptying in man.
Authors: L A Houghton, F Hickson, N W Read
Journal: Gut (1987)

The gastric emptying of two radiolabelled pancake meals of identical composition, but different consistency, was compared with the rates at which they could be broken down in vitro by mechanical agitation in a solution of either acid-pepsin or saline. Neither of the pancake meals were broken up within 150 minutes by mechanical agitation in a normal saline medium, but both were disrupted in the presence of acid-pepsin, the light consistency pancake being broken up more rapidly than the heavy consistency pancake (0.5 +/- 0.1 v 0.2 +/- 0.1% radioactivity appearing in the bathing medium per minute, p less than 0.01). Under normal conditions, the pattern and rate of gastric emptying of both meals was similar. Stimulating acid secretion with pentagastrin (6 micrograms/kg bodyweight sc) delayed the onset of emptying of both pancakes and tended to increase the slope of emptying. Under these conditions, the denser pancake was emptied more slowly than the lighter pancake because of an increase in the lag period. Thus the data did not confirm the hypothesis that the rate of emptying of disruptible solid food from the stomach under normal conditions of acid secretion is influenced by the ease with which it can be broken down by mechanical agitation in an acid-pepsin medium. The trend for an accelerated rate of emptying after administration of pentagastrin, however, may well be explained by the increased rate of disruption of the food in the presence of acid, but the longer lag periods are more compatible with inhibition of gastric emptying caused by free acid in the duodenum.
Bisphenol A Induces a Profile of Tumor Aggressiveness in High-Risk Cells from Breast Cancer Patients
Authors: Shanaz H. Dairkee, Junhee Seok, Stacey Champion, Aejaz Sayeed, Michael Mindrinos, Wenzhong Xiao, Ronald W. Davis, William H. Goodson
Journal: Cancer Research (2008)

Abstract Breast cancer outcome is highly variable. Whether inadvertent exposure to environmental xenobiotics evokes a biological response promoting cancer aggressiveness and a higher probability of tumor recurrence remains unknown. To determine specific molecular alterations which arise in high-risk breast tissue in the presence of the ubiquitous xenoestrogen, bisphenol A (BPA), we used nonmalignant random periareolar fine-needle aspirates in a novel functional assay. Early events induced by BPA in epithelial-stromal cocultures derived from the contralateral tissue of patients with breast cancer included gene expression patterns which facilitate apoptosis evasion, endurance of microenvironmental stress, and cell cycle deregulation without a detectable increase in cell numbers. This BPA response profile was significantly associated with breast tumors characterized by high histologic grade (P &amp;lt; 0.001) and large tumor size (P = 0.002), resulting in decreased recurrence-free patient survival (P &amp;lt; 0.001). Our assays show a biological “fingerprint” of probable prior exposure to endocrine-disrupting agents, and suggest a scenario in which their presence in the microenvironmental milieu of high-risk breast tissue could play a deterministic role in establishing and maintaining tumor aggressiveness and poor patient outcome. [Cancer Res 2008;68(7):2076–80]
Abstract P3-06-18: The health of women study: A novel approach to the cohort study
Authors: SM Love, N Sykes, CA Fischetti, J Sullivan-Halley, J Clague, L Bernstein
Journal: Cancer Research (2013)

Abstract PURPOSE: The purpose of the Health of Women (HOW) Study is to examine risk factors for breast cancer and factors that may contribute to long-term survivorship through an innovative online system that allows for participant engagement and data sharing with the research community. METHODS: The HOW Study is conducted through online and mobile phone platforms. Questionnaires are developed in our custom built survey tool and are available for completion on the study's website. The system allows for automated skip patterns within questionnaires and collection of data directly into a SQL database. The cohort is open to anyone 18 years or older; recruitment sources include the Love/Avon Army of Women and the general public. Participants will be given the opportunity to pose questions they would like to see answered. The HOW Study is also a novel resource allowing outside researchers to submit questions to be incorporated into HOW questionnaires and creating a data sharing platform that facilitates researcher access to HOW data after an application process. RESULTS: The HOW Study launched October 2012 and currently has 41,800 participants from across the nation and the globe. We have released 1 baseline questionnaire and breast cancer-specific questionnaires to capture diagnosis and treatment with greater than 90% completion rate for each. CONCLUSION: We have shown that we can recruit and engage participants in an online cohort study. We believe that this study has the potential to transform epidemiologic research by engaging both participants and the research community. Our second baseline questionnaire will launch in the summer of 2013, which will give us the opportunity to increase enrollment and assess retention. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-18.
Abstract 5098: A mouse DLL4 cross-reactive variant of MEDI0639 disrupts functional vessel formation and inhibits tumor growth in preclinical models.
Authors: Song H. Cho, David W. Jenkins, Patrick Strout, Martin Korade, Haihong Zhong, Ching Ching Leow, Shannon Breen, Jon Chesebrough, Nicholas Holoweckyj, Ivan Inigo, Gennady Gololobov, Ping Tsui, Kimberly Cook, Melissa Damschroder, Meggan Czapiga, Philip Brohawn, Jiaqi Huang, Sally-Ann Ricketts, Juliana Maynard, Adeela Kamal
Journal: Cancer Research (2013)

Abstract Delta-like ligand 4 (DLL4) is a membrane bound ligand for Notch receptors essential for functional vessel formation during development and angiogenesis. We have shown previously that MEDI0639, a human anti-DLL4 antibody, has potent in vitro and in vivo activity in blocking DLL4-Notch interaction. However, because MEDI0639 has low binding affinity to mouse DLL4, to enable in vivo pharmacology studies using xenograft tumor models in mice, MEDI0639 was engineered to bind more strongly to mouse DLL4. The resulting affinity-optimized variant antibody (anti-mDLL4 mAb) bound with high affinity to both human and mouse DLL4 and maintained binding specificity to DLL4. In a number of human cancer xenograft models in nude mice, the MEDI0639 variant antibody markedly inhibited the growth of tumors. qRT-PCR analysis using the Fluidigm platform showed decreases in mouse genes downstream of the Notch signaling pathway at efficacious doses, indicating on-target antibody effect on tumor vasculature. In addition, IHC and imaging analysis of xenograft tumors from the anti-DLL4 mAb dosed animals showed a dose-dependent increase in microvessel density and decrease in tumor perfusion compared to the control groups. In summary, we describe here the generation of mouse and human DLL4 cross-reactive antibody and the utilization of this antibody in demonstrating a positive correlation between the anticipated mechanism of action of DLL4 blockade on vasculature and inhibition of tumor growth. Citation Format: Song H. Cho, David W. Jenkins, Patrick Strout, Martin Korade, Haihong Zhong, Ching Ching Leow, Shannon Breen, Jon Chesebrough, Nicholas Holoweckyj, Ivan Inigo, Gennady Gololobov, Ping Tsui, Kimberly Cook, Melissa Damschroder, Meggan Czapiga, Philip Brohawn, Jiaqi Huang, Sally-Ann Ricketts, Juliana Maynard, Adeela Kamal. A mouse DLL4 cross-reactive variant of MEDI0639 disrupts functional vessel formation and inhibits tumor growth in preclinical models. [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 5098. doi:10.1158/1538-7445.AM2013-5098
B-Cell-Delivered Gene Therapy Induces Functional T Regulatory Cells and Leads to a Loss of Antigen-Specific Effector Cells
Authors: Jonathan Skupsky, Ai-Hong Zhang, Yan Su, David W Scott
Journal: Molecular Therapy (2010)

Previous reports have shown that B-cell-mediated gene therapy can induce tolerance in several animal models for autoimmune diseases and inhibitory antibody formation in hemophilia A mice. We know from our previous work that the induction of tolerance following B-cell therapy is dependent upon CD25(+) regulatory T cells (Tregs). To extend these studies and identify the effects of this gene therapy protocol on the target CD4 T cells, we have adapted in vitro suppression assays using Tregs isolated from treated and control mice. Using carboxyfluorescein succinimidyl ester (CFSE) dilution as a measure of T-cell responsiveness to FVIII, we show that CD25(+) Tregs from treated mice are more suppressive than those from control animals. To monitor the induction of antigen-specific Tregs, we repeated these studies in ovalbumin (OVA) peptide-specific DO11.10 T-cell receptor (TCR) transgenic mice. Tregs from DO11.10 mice treated with a tolerogenic OVA-Ig construct are better than polyclonal Tregs at suppressing the proliferation of responder cells stimulated with OVA peptide 323-339 (pOVA). Furthermore, we show that following B-cell therapy, there is an increase in antigen-specific FoxP3(+) Tregs, and there is also a distinct decrease in antigen-specific CD4(+) effector T cells. These changes in the lymphocyte population shift the balance away from effector function toward a tolerogenic phenotype.
Histopathology of Salivary Gland Lesions
Authors: Jerry M. Gray
Journal: JAMA (1966)

The author has provided us with a thoroughly illustrated book, intended for physicians, dentists, and students, covering the neoplastic and non-neoplastic lesions of salivary glands including a chapter on their embryology and histology. Histologic features have been emphasized, and the author wisely excluded "those lesions that are so rare that there is doubt as to their existence...." Presumably he means doubt as to their classification and biologic behavior. Well organized, the book proceeds from embryology and histology through inflammatory lesions to neoplasms. The text is brief and concise, and the author relies heavily on the 267 illustrations to cover the main ideas involved. Although many of the photomicrographs are clear, unfortunately a significant number lack good resolution, and their usefulness is greatly diminished. The captions of the photographs are generally very well done. The close association of lymphoid tissue and glandular elements in the embryology and histology of salivary glands,
Calcium and Phosphorus Metabolism in Breast Cancer.
Authors: B. Gardner
Journal: Annals of Internal Medicine (1962)

s1 April 1962Calcium and Phosphorus Metabolism in Breast Cancer.B. Gardner, M.D.B. Gardner, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-4-693_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptParticipation in the National Cooperative Study of the effect of experimental steroids on advanced breast cancer required classification of sites of metastases (osseous or soft tissue) and evaluation of activity (objective regression, progression, or static) in each patient at four to six-week intervals. Regression was defined as: [1] significant shrinkage of measurable lesions, [2] calcification of osseous metastases, [3] failure of new lesions to appear, and [4] confirmation by two disinterested experts. Simultaneous measurement of serum and urinary calcium levels permitted correlation with clinical status.Although hypercalcemia occurred more commonly in association with osseous disease, it also was found in... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Daly City, Calif. (BS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1962Volume 56, Issue 4Page: 693-694KeywordsBreast cancerCalciumHypercalcemiaLesionsPhosphorusSoft tissuesSteroids Issue Published: 1 April 1962 PDF downloadLoading ...
Thiol/disulfide exchange is a prerequisite for CXCR4-tropic HIV-1 envelope-mediated T-cell fusion during viral entry
Authors: Ingrid Markovic, Tzanko S. Stantchev, Karen H. Fields, Linda J. Tiffany, Melanija Tomiç, Carol D. Weiss, Christopher C. Broder, Klaus Strebel, Kathleen A. Clouse
Journal: Blood (2003)
421. Killing of Normal Cells Combined with TLR Engagement and CD40 Ligation Generates Autoimmune T Cell Reactivity Sufficient To Treat Large Established Tumors
Authors: Luis Sanchez-Perez, Gregory Daniels, Timothy Kottke, Rosa Maria Diaz, Jill Thompson, Heung Chong, Alan Melcher, Richard Vile
Journal: Molecular Therapy (2006)

We have shown that inflammatory killing of normal melanocytes by intradermal injection of plasmids expressing HSVtk from a melanocyte specific promoter, along with hsp70 from a CMV promoter, cures small established B16 melanomas. However, destruction of normal cells is also accompanied by induction of regulatory T cells which, through a TGF-β-dependent mechanism, restrain the activity of CD8+ T cells specific for melanocyte/ melanoma associated antigens, restrict induction of autoimmunity and inhibit memory against melanoma re-challenge. Hsp70 is critical for this effect in vivo. We have now shown that hsp70 expression locally at the site of melanocyte killing induces TNF-α which is associated with migration of ClassII+ve/CD11c+ cells to the draining lymph nodes. These CD11c+ve cells can directly activate naive T cells against melanocyte expressed antigens. The ability of these cells to prime T cell responses against melanocyte expressed antigens is lost in TNF-α-/- mice. Moreover, therapy is lost in TLR4 knockout mice indicating that hsp70 acts through stimulation of Toll Like Receptors on cells locally resident in the skin. When a plasmid expressing CD40L was co-expressed with Ty r- HSVtk+hsp70, this regimen was able to cure large, 9 day established tumors with the same number of plasmid injections. CD40L plasmid, along with melanocyte killing, increased the frequency (by tetramer staining) and potency (IFN-γ ELISPOT) of antigen specific T cells compared to the use of Tyr-HSVtk and hsp70 alone and induces significant splenomegaly in treated mice. Moreover, animals treated with inflammatory melanocyte killing+pCD40L developed aggressive autoimmune vitiligo and alopecia, and cured mice developed immunological memory against B16 rechallenge. CD40L plasmid caused depletion of CD4+CD25+ Treg cells from the spleens and LN of mice 8 days following the first of three id injections, indicating a novel mechanistic link between the magnitude of anti melanoma T cell responses, CD40 ligation and Treg activity/survival. Finally, we have now extended these studies to show that the inflammatory killing of normal prostate tissue in vivo by a single dose of adenoviral- mediated gene delivery can also cure established TrampC2 tumors seeded subcutaneously in immunocompetent mice. Therapy was associated with weight reductions of about 50% of prostates from cured mice, indicating induction of a potent anti-prostate immune reaction. Taken together, our data show that by manipulating in vivo mechanisms which normally restrain autoimmune responses, increased anti-tumor responses can be induced following the killing of normal cells. However, such strategies also run the risk of increasing autoimmune related side effects.
Variations in the 5-Hydroxytryptamine Type 3B Receptor Gene as Predictors of the Efficacy of Antiemetic Treatment in Cancer Patients
Authors: Pierre-Benoit Tremblay, Rolf Kaiser, Orhan Sezer, Nadja Rösler, Claudia Schelenz, Kurt Possinger, Ivar Roots, Jürgen Brockmöller
Journal: Journal of Clinical Oncology (2003)

Purpose: Serotonin (5-hydroxytryptamine type 3 [5-HT 3 ]) receptor antagonists have substantially reduced but not eliminated nausea and vomiting in patients undergoing cancer chemotherapy. They act through specific binding to the 5-HT 3A , 5-HT 3B receptor complex. The 5-HT 3B subunit seems to be most important for its functionality. We hypothesized that patients with genetic variations in the 5-HT 3B receptor gene might respond differently to antiemetic treatment. Patients and Methods: We included 242 cancer patients on their first day of chemotherapy. Nausea and vomiting were documented before and twice during the chemotherapy using standardized interviews and visual analog scales. We sequenced the entire 5-HT 3B receptor gene, including the 5` flanking region and at least a 20–base pair intronic sequence of each intron-exon splice site of all patients. Results: Approximately 30% of all patients suffered from nausea or vomiting. Sequencing of the 5-HT 3B receptor gene revealed 13 polymorphisms: two of them were amino acid exchanges (Tyr129Ser, Ala223Thr) and two were deletion variants. In both observation periods, patients homozygous for the −100_−102delAAG deletion variant of the promotor region experienced vomiting more frequently than did all the other patients. Conclusion: A more efficient antiemetic treatment with 5-HT 3 receptor antagonists might be possible on a pharmacogenetic basis. However, only a small fraction of the therapeutic failure is explained by the −AAG deletion variant of the 5-HT 3B receptor gene. Additional clinical and biochemical studies are needed to confirm the association.
Therapy of Fluid and Electrolyte Disorders
Authors: W. ARTHUR BURKE
Journal: Annals of Internal Medicine (1975)

Comments and Corrections1 June 1975Therapy of Fluid and Electrolyte DisordersW. ARTHUR BURKE, PHARM.D.W. ARTHUR BURKE, PHARM.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-82-6-844 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The paper by Lindeman and Papper (Ann Intern Med82:64-70, 1975), a fine review of the therapy of fluid and electrolyte disorders, is unfortunately made potentially dangerous by what appear to be some gross typographical errors. I hope the following will be helpful in correcting some misinformation conveyed by an otherwise useful, and definitely much needed, paper.With regard to calcium, calcium gluconate, available as 10 ml of a 10% solution, provides approximately 4.6 meq calcium ion (Ca++) per 1 g of calcium gluconate,not50 meq of Ca++ as reported. This may be calculated as follows:...Reference Reference1. SCHWARTZWATERS WW: Lactate versus bicarbonate. Am J Med 32:831-834, 1962 CrossrefMedlineGoogle Scholar1. GOLDSMITHINGBAR RS: Inorganic phosphate treatment of hypercalcemia of diverse etiologies. N Engl J Med 274:1-7, 1966 CrossrefMedlineGoogle Scholar1. WOODSALBERTI HK: Dangers of intravenous fructose. Lancet 2:1354-1357, 1972 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: W. ARTHUR BURKE, PHARM.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1975Volume 82, Issue 6Page: 844-846KeywordsCalciumFructoses ePublished: 12 March 2020 Issue Published: 1 June 1975 PDF downloadLoading ...
False-Positive Reaction to VDRL Test With Prozone Phenomena
Authors: Kirk D. Wuepper
Journal: JAMA (1966)

A patient with lymphosarcoma had a VDRL test reactive at 1:256. A prozone phenomenon was also present. The nontreponemal test result was shown to be a false-positive reaction by nonreactive Treponema pallidum immobilization and fluorescent treponemal antibody absorption tests. High-titer serologic tests for syphilis are uncommon, and prozone reactions are previously unrecorded in the false-positive reactor.