tbuckley/cabot-search huggingface dataset:
Globular hepatic amyloid–-an unusual morphologic presentation
Authors: Gary C. Kanel, Toshikazu Uchida, Robert L. Peters
Journal: Hepatology (1981)

Hepatic amyloid, when identified, is usually located in the sinusoids, portal tracts, and arterioles. We report 14 cases of hepatic amyloidosis where eosinophilic globules having the histochemical and electron microscopic features of classic amyloid were found. The globules were round to oval, 5 to 40 μm in diameter, and were found within the space of Disse as well as aggregated within the portal tracts. There were no distinctive clinical or laboratory features distinguishing this type of amyloidosis from classic hepatic amyloidosis. However, there were no cases of multiple myeloma and only one of benign monoclonal gammopathy. All seven patients who were studied at postmortem examination had systemic (nonglobular) amyloidosis. This form of hepatic amyloidosis is probably not an early form of the disease but is an original but rare presentation of hepatic amyloid deposition.
Opioids for low back pain
Authors: R. A. Deyo, M. Von Korff, D. Duhrkoop
Journal: BMJ (2015)

Back pain affects most adults, causes disability for some, and is a common reason for seeking healthcare. In the United States, opioid prescription for low back pain has increased, and opioids are now the most commonly prescribed drug class. More than half of regular opioid users report back pain. Rates of opioid prescribing in the US and Canada are two to three times higher than in most European countries. The analgesic efficacy of opioids for acute back pain is inferred from evidence in other acute pain conditions. Opioids do not seem to expedite return to work in injured workers or improve functional outcomes of acute back pain in primary care. For chronic back pain, systematic reviews find scant evidence of efficacy. Randomized controlled trials have high dropout rates, brief duration (four months or less), and highly selected patients. Opioids seem to have short term analgesic efficacy for chronic back pain, but benefits for function are less clear. The magnitude of pain relief across chronic non-cancer pain conditions is about 30%. Given the brevity of randomized controlled trials, the long term effectiveness and safety of opioids are unknown. Loss of long term efficacy could result from drug tolerance and emergence of hyperalgesia. Complications of opioid use include addiction and overdose related mortality, which have risen in parallel with prescription rates. Common short term side effects are constipation, nausea, sedation, and increased risk of falls and fractures. Longer term side effects may include depression and sexual dysfunction. Screening for high risk patients, treatment agreements, and urine testing have not reduced overall rates of opioid prescribing, misuse, or overdose. Newer strategies for reducing risks include more selective prescription of opioids and lower doses; use of prescription monitoring programs; avoidance of co-prescription with sedative hypnotics; and reformulations that make drugs more difficult to snort, smoke, or inject.
Changes in the antigenic properties of connective tissue in the skin of embryonic rats during development.
Authors: D G Scott, N R Rowell
Journal: Annals of the Rheumatic Diseases (1967)

Inflammation may contribute to upper airway pathophysiology in obstructive sleep apnoea (OSA). Our objective was to compare upper airway pro-inflammatory cytokine expression, oxidative stress and connective tissue deposition in severe (n=25) <i>versus</i> mild (n=17) OSA patients. Upper airway surgical specimens were separated by predominance of either mucosal or muscle tissue. Expression levels for Interleukin-1α, Interleukin-6, Interferon-γ, RANTES, Transforming Growth Factor-β, and L-Selectin were measured by Ribonuclease Protection Assay. Oxidative stress was assessed <i>via</i> protein carbonyl group detection by immunoblotting. Histochemistry was employed for immunolocalization of selected cytokines, and connective tissue morphometry. In the severe OSA group, expression of Interleukin-1α, Interleukin-6 and Transforming Growth Factor-β was significantly higher in mucosa-predominant tissues, whereas in muscle-predominant specimens, RANTES expression was greater in severe OSA. Increased protein carbonylation was observed in severe OSA within both mucosal and muscle compartments. Immunohistochemistry localized Transforming Growth Factor-β to submucosal and perimuscular inflammatory cells, while Interleukin-6 was primarily localized to myocytes. Consistent with the pro-fibrotic cytokine profile observed in mucosa-predominant tissue, morphometric analysis revealed greater submucosal and perimuscular connective tissue in severe OSA subjects. There is increased pro-inflammatory and pro-fibrotic cytokine expression, oxidative stress, and connective tissue deposition in upper airway tissues from severe <i>versus</i> mild OSA patients.
Urinary kallikrein in rats bred for their susceptibility and resistance to the hypertensive effect of salt. A new radioimmunoassay for its direct determination.
Authors: O A Carretero, V M Amin, T Ocholik, A G Scicli, J Koch
Journal: Circulation Research (1978)

Urinary kallikrein was measured in rats bred to be susceptible (S) or resistant (R) to the hypertensive effect of salt. To determine kallikrein, three different methods were used: (1) a new direct radioimmunoassay (RIA) for the enzymic protein: (2) a method based on the capability of kallikrein, when incubated with kininogen, to generate kinins which were then measured by RIA (kininogenase activity); and (3) a method based on the capability of kallikrein to break the ester bond of p-tosyl-L-arginine methyl ester (HCl (TAMe). A significant correlation ( r = 0.90) was found between the direct RIA and the kininogenase method. It was found that urinary kallikrein was significantly decreased in the S as compared to the R rats by the use of these three methods. Urinary kallikrein in the S rats was much lower when measured by the kininogenase method than by direct RIA or esterolytic assay. This difference could be due to excretion of pre-kallikrein and/or kallikrein bound to an inhibitor (inactive kallikrein). It is suggested that the decrease of urinary kallikrein excretion (active and inactive) in the S rats could be a consequence of a genetic defect that may affect the development of hypertension perhaps through the alteration of sodium and water excretion by the kidney.
An interleukin-2 receptor gamma chain mutation with normal thymus morphology.
Authors: N Sharfe, M Shahar, C M Roifman
Journal: Journal of Clinical Investigation (1997)

One of the most common human immunodeficiencies is an X-linked condition arising from mutations of the gamma subunit of the interleukin-2 receptor (IL-2Rgamma). The IL-2Rgamma protein is one chain of the heterotrimeric (alpha, beta, gamma) IL-2 receptor, but also participates in the formation of the IL-4, 7, 9, and 15 receptor complexes. The diagnosis of X-linked SCID is usually relatively simple due to the distinctive immunological presentation; IL-2Rgamma-deficient patients typically lacking mature T lymphocytes (T-B+). However, it is becoming clear that this merely represents one extreme of a potential range of clinical presentations. We describe here a novel mutation of the human IL-2Rgamma chain (R222C) resulting in an unusual immunological phenotype. Although clinically immunodeficient, this patient has normal numbers of peripheral T and B cells, responds normally to mitogenic stimuli, and unusually, has a normal thymus gland. This IL-2Rgamma mutation is distinctive in that the protein is sufficiently stable to be expressed at the cell surface. While the T cell receptor repertoire appears complete, suggesting normal T cell differentiation occurs, patient T cells demonstrate a reduced ability to bind IL-2 and this appears sufficient to cause a deficiency in their ability to participate in antigenic responses. Early clinical recognition of this phenotype is critical as a delay in diagnosis may result in a fatal infection.
Unilateral Hypacusis and Facial Swelling
Authors: Sidney P. Kadish
Journal: JAMA (1971)

Dr. Robert A. Novelline: This 63-year-old white woman was admitted to the Massachusetts Eye and Ear Infirmary because of painless swelling of the left eyelids and left cheek of 1 1/2 years' duration. One year prior to admission, she noted decreased auditory acuity on the left side. The auditory symptoms and edema responded to a course of corticosteroids. Physical examination revealed these findings on the left side: marked edema of the lower eyelid, slight swelling of the upper lid, slight proptosis, a mass in the upper part of the buccogingival area, and swelling of the cheek. Nasopharyngoscopy showed swelling of the orifice of the left eustachian tube and a smooth, bulging mass in the left vault of the nasopharynx. The left maxillary antrum transilluminated poorly. No lymph nodes were palpable in the neck. Roentgenograms of the paranasal sinuses and skull were obtained. <h3>Discussion</h3> Dr. Paul F. J. New: In the
Differentiation and Immune Regulation of IL-9−Producing CD4<sup>+</sup> T Cells in Malignant Pleural Effusion
Authors: Zhi-Jian Ye, Qiong Zhou, Wen Yin, Ming-Li Yuan, Wei-Bing Yang, Xian-Zhi Xiong, Jian-Chu Zhang, Huan-Zhong Shi
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: IL-9–producing CD4+ T cells (Th9 cells) have been reported to be involved in inflammation and immune diseases. However, the involvement of Th9 cells in malignancy has not been investigated.Objectives: To elucidate the mechanism by which Th9 cells differentiate in malignant pleural effusion (MPE) and to explore the immune regulation of Th9 cells on lung cancer cells.Methods: Distribution of Th9 cells in relation to Th17 and Th1 cells in both MPE and blood were determined. The effects and mechanisms of proinflammatory cytokines and regulatory T cells on differentiation of Th9 cells in vitro were explored. The impacts and signal transductions of IL-9, IL-17, and IFN-γ on lung cancer cell lines were also investigated.Measurements and Main Results: The numbers of Th9, Th17, and Th1 cells were all increased in MPE when compared with blood. The increase in Th9 cells in MPE was due to the promotion by cytokines and regulatory T cells. By activating STAT3 signaling, both IL-9 and IL-17 substantially promoted the proliferation and migratory activity of lung cancer cells, whereas IFN-γ, which activated STAT1 signaling, was noted to suppress lung cancer cell proliferation and migration. IFN-γ could induce lung cancer cell apoptosis. Moreover, IL-9 and IFN-γ, but not IL-17, could strongly facilitate intercellular adhesion of lung cancer cells to pleural mesothelial cell monolayers.Conclusions: Our data revealed that Th9 cells were increased in MPE and that Th9 cells exerted an important immune regulation on lung cancer cells in human tumor environment.
Persistence of decreased T-helper cell function in industrial workers 20 years after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Authors: T Tonn, C Esser, E M Schneider, W Steinmann-Steiner-Haldenstätt, E Gleichmann
Journal: Environmental Health Perspectives (1996)

In experimentally exposed animals 2,3,7,8-tetrachlorodibenzo-n-dioxin (TCDD) causes severe immunosuppression. However, the overall susceptibility of humans for the different pathological effects of TCDD has remained unclear. We examined the long-term effects of TCDD in 11 industrial workers who were exposed to high doses of TCDD for several years 20 years ago. Current TCDD body burdens were still at least 10 times higher (between 43 and 874 pg/g blood far) in these exposed persons than in the average German population. To evaluate possible TCDD-induced changes in the percentage of different lymphocyte subsets, we determined a large panel of lymphocyte subsets in the blood by flow cytometric analysis. Immunocompetence of T-and B-lymphocytes was tested by nitrogen (phytohemagglutinin, pokeweed mitogen)- induced lymphoproliferation assays and by assays using sensitive mixed-lymphocyte cultures. No significant differences could be detected between the individuals tested and controls for surface marker distribution or mitogen-induced lymphoproliferation TCDD-exposed subjects showed a reduced response to human lymphocyte antigen-allogeneic lymphocytes and interleukin-2-boosted proliferation. Responder cells of the dioxin-exposed persons proliferated less in response to irradiated stimulator cells (p < or = 0.05), and the third-party mixed lymphocyte reaction against unirradiated stimulator cells revealed suppressive activity in the responder cell fraction compared to the controls (p < or = 0.01). Furthermore, the capacity of a pool of T cells isolated from TCDD-exposed subjects to proliferate upon interleukin-2 stimulation was significantly diminished (p < or = 0.05). TCDD has a long-term immunosuppressive-effect on T-helper cell function, which is mediated more likely by a reduced functionality of individual cells rather than by a reduction in absolute cell numbers in the peripheral blood.
Prevention and Treatment of Experimental Estrogen Receptor–Negative Mammary Carcinogenesis by the Synthetic Triterpenoid CDDO-Methyl Ester and the Rexinoid LG100268
Authors: Karen Liby, Renee Risingsong, Darlene B. Royce, Charlotte R. Williams, Mark M. Yore, Tadashi Honda, Gordon W. Gribble, William W. Lamph, Nicola Vannini, Ilaria Sogno, Adriana Albini, Michael B. Sporn
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To test whether the triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) and the rexinoid LG100268 (268) prevent the formation of estrogen receptor (ER)–negative mammary tumors or either arrest the growth or cause regression of established tumors in MMTV-neu mice. Experimental Design: For prevention, mice were fed control diet, CDDO-Me (60 mg/kg diet), 268 (20 mg/kg diet), or the combination for 45 weeks. For treatment, mice with established tumors at least 4 mm in diameter were fed control diet, CDDO-Me (100 mg/kg diet), 268 (60 mg/kg diet), or the combination for 4 weeks. Results: CDDO-Me and 268 significantly delayed the development of ER-negative tumors, with a 14- and 24-week delay, respectively, compared with the control group for the time required to reach 50% tumor incidence. The combination of CDDO-Me and 268 was significantly more potent than the individual drugs, as only one tumor was found in the combination group, after 45 weeks on diet, at which time all control animals had tumors. Treating established tumors with CDDO-Me arrested the growth of 86% of the tumors, and 268 induced tumor regression in 85% of tumors. CDDO-Me and 268 target different signaling pathways and cell types. CDDO-Me inhibited constitutive STAT3 phosphorylation and the degradation of IKBα in ER-negative breast cancer cells, whereas 268 blocked IKBα degradation and the release of interleukin-6 in RAW264.7 macrophage-like cells, inhibited the ability of endothelial cells to organize into networks, and blocked angiogenesis in vivo. Conclusions: CDDO-Me and 268 are useful as individual drugs to prevent ER-negative mammary tumorigenesis and to treat established tumors. They synergize when used in combination for prevention.
923. Combining In Situ Gene Therapy with Radiotherapy and Hormonal Therapy in the Treatment of Stage D1 Prostate Cancer
Authors: Tetsuo Fujita, Bin S. Teh, Terry L. Timme, Gustavo Ayala, Wei-Yuan Mai, Takefumi Satoh, Nobuyuki Kusaka, Koji Naruishi, Ken-ichi Tabata, Estuardo Aguilar-Cordova, Thomas Wheeler, E. Brian Butler, Timothy C. Thompson
Journal: Molecular Therapy (2006)

Introduction: Clinical trial of combination adenoviral vector mediated Herpes Simplex Virus-thymidine kinase (HSV-tk) + valacyclovir (VCV) in situ gene therapy with radiotherapy (RT) and hormonal therapy was conducted for Stage D1 prostate cancer. We now report the safety, efficacy, and immune responses using this approach. Methods: Five patients with Stage D1 prostate cancer were treated as follows: Gene therapy: 3 separate intraprostatic injections of AdHSV-tk were performed on days 0, 56, and 70. Each injection was followed by 2 weeks of VCV. RT to pelvic lymphatics and prostate was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy: lupron and flutamide were initiated on day 0 for 4 months or 2 years. Toxicity was assessed using CTEP and RTOG toxicity scores. Peripheral blood lymphocytes were analyzed by fluorescent antibody cell sorting (FACS) after the incubation with dual color labeled antibody pairs: CD45/CD14, CD3/CD19, CD3/CD8, CD3/CD4, CD8/HLA-DR, CD4/HLA-DR, CD3/HLA-DR, and CD3/CD56+CD16. PSA, prostate biopsy, and FACS samples were taken at selected intervals. ASTRO consensus definition was used for PSA failure. Results: Median age was 50 years and median follow-up for the entire group was 29 months. Mean and median pre-treatment PSA were 97.3 and 16.9 ng/ml (range; 2.5–374 ng/ml). Gleason score was 8 in 2 patients and 9 in the other 3 patients. Three of the 5 patients had biochemical failure at 3, 3, and 7.7 months: 2 patients had distant failure in the bones and 1 patient had failure in the para- aortic lymph nodes outside radiation treatment portal. Prostate biopsies however revealed no evidence of residual carcinoma in all cores. The pre-treatment mean percentages of activated CD8+ (DR+CD8+) T cells and activated CD4+ (DR+CD4+) T cells were 12.0% and 5.3% respectively. Four months after the initial treatment, the mean percentages of DR+CD8+ T cells and DR+CD4+ T cells increased to 32.7% and 18.8% (P=0.0431) respectively. No grade 3 or higher toxicity was seen. The GU and GI toxicity profiles are no different from those of patients treated with RT alone. Conclusions: We present evidence of safety and efficacy using this combined radio-gene-hormonal therapy approach for Stage D1 prostate cancer. These results also suggest the potential for activation of cell-mediated immune response using this combined therapy. Current efforts are aimed to improve systemic control by maximizing activation of anti-tumor immune response in these patients via radio-gene therapy.
Abstract 11724: Increased Heart Rate as a Significant Prognostic Factor in Patients with Heart Failure with Preserved Ejection Fraction -A Report from the CHART-2 Study-
Authors: Tsuyoshi Takada, Yasuhiko Sakata, Satoshi Miyata, Jun Takahashi, Kotaro Nochioka, Masanobu Miura, Hiroaki Shimokawa
Journal: Circulation (2012)
Letter from Yekaterinburg
Authors: Rolf A. Streuli
Journal: Annals of Internal Medicine (1996)

The Russian city of Yekaterinburg, known as Sverdlovsk before the influence of perestroika, lies at the eastern foot of the Ural Mountains on the border between Europe and Asia.It was the site of large armaments factories, most of which are now closed, but the area continues to feel the aftermath of their heavy pollution. The annual Congress of the Russian Society of Internal Medicine was held here in 1995 and was attended by physicians from all corners of this vast country. Leaders in the field of internal medicine from Russia presented state-of-the-art papers on many aspects of the theme of the conference, Emergencies in Internal Medicine. The problem of the acquired immunodeficiency syndrome was also discussed, but this subject is still taboo as far as the official health authorities are concerned. The Russian physicians talked about how they deplored the great shortage of disposable medical equipment. One of the most serious health problems in Russia is alcoholism; surprisingly, this problem was hardly mentioned at the congress. An open international exchange of information is again possible in Russia, but financial considerations restrict attendance at meetings abroad and the availability of professional journals domestically.
Evaluation of Protective Effect of Fenoterol in Allergen‐Induced Bronchospasm
Authors: G. D'Amato, M. Schiano, G. Balzano, G. Gocco, G. Melillo
Journal: Allergy (1983)

The purpose of this study was to determine the intensity and duration of the protective effect of fenoterol (200 micrograms) in allergen-induced bronchospasm and to compare its effect with that of DSCG (20 mg). Twelve atopic-asthmatic patients, with ages ranging from 10 to 41 years, participated in the study. At the time of the study their symptoms were well controlled without the use of anti-asthmatic drugs and their FEV1 was greater than 80% of predicted and did not vary by more than 10% on each study day. The study was a double-blind cross over trial. Each drug was given separately at 1 week intervals according to an appropriate random plan. During the treatment the patients were given two puffs of metered dose aerosol and a capsule of inhalation powder. Each patient was given aerosol with test drug and placebo aerosol alternately, according to the double-blind method. The allergen was given 90 min after the administration of the drugs, and parameters of the respiratory function were controlled over a period of 6 h. Subsequently, the protective effect of 200 micrograms fenoterol administered 4 h before the allergen was studied openly, and showed that fenoterol possesses a protective effect in allergen-induced bronchospasm. This effect, although slightly reduced, persists even when the allergen is administered 4 h later.
AN ARTICLE CONTRIBUTED TO AN ANNIVERSARY VOLUME IN HONOR OF DR. JOSEPH HERSEY PRATT
Authors: ROBERT L. LEVY
Journal: Annals of Internal Medicine (1937)

Article1 November 1937AN ARTICLE CONTRIBUTED TO AN ANNIVERSARY VOLUME IN HONOR OF DR. JOSEPH HERSEY PRATTCOFFEE AS A CAUSE OF CARDIAC PAIN*ROBERT L. LEVY, M.D., F.A.C.P.ROBERT L. LEVY, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-11-5-833 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThere are many disturbances, both anatomical and physiological, which may cause pain in the region of the heart. To differentiate them and, in a given case, to determine the particular condition giving rise to discomfort, is the first requisite in diagnosis. The accurate definition of etiology often makes possible the distinction between a mild and a grave malady; it is essential for the institution of effective therapy.As a cause of cardiac pain the drinking of coffee has received but scant attention, though briefly mentioned by some of the older clinicians. For example, Krehl1states that "poisoning by coffee may...References1. KREHL L: Die Erkrankungen des Herzmuskels, 1913, Alfred Hölder, Wien und Leipzig, p. 97. Google Scholar2. ALLBUTT C: Diseases of the arteries, including angina pectoris, 1915, Macmillan and Co., London, p. 500. Google Scholar3. SOLLMANN T: A manual of pharmacology and its applications to therapeutics and toxicology, 1936, W. B. Saunders Co., Philadelphia and London, p. 269. Google Scholar4. LEVY RL: Arteriosclerosis, including thrombosis, of the coronary arteries. Chapter VIII in Diseases of the coronary arteries and cardiac pain, edited by R. L. Levy, 1936, Macmillan and Co., New York, p. 217. Google Scholar5. See reference 3, pp. 255-273. Google Scholar6. BROWLONGBEATTIE GRCNJ: Irregularities of the heart under chloroform; their dependence on the sympathetic nervous system, Jr. Am. Med. Assoc., 1930, xcv, 715. CrossrefGoogle Scholar7. DIKSHIT BB: The production of cardiac irregularities by excitation of the hypothalamic centers, Jr. Physiol., 1934, lxxxi, 382. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ROBERT L. LEVY, M.D., F.A.C.P.Affiliations: New York, N. Y.*Received for publication July 28, 1937.From the Department of Medicine, College of Physicians and Surgeons, Columbia University, and the Medical Clinic of the Presbyterian Hospital. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1937Volume 11, Issue 5Page: 833-837KeywordsCoffeeEtiologyHeartHospital medicineSurgeons ePublished: 1 December 2008 Issue Published: 1 November 1937 PDF downloadLoading ...