tbuckley/cabot-search huggingface dataset:
672. The Effect of Serine Protease Inhibitor 6 (SPI-6) Gene Transfer on a Mouse Model of Sjögren's Syndrome
Authors: Fumi Mineshiba, Beatrijs M. Lodde, Jianghua Wang, Livia A. Casciola-Rosen, Antony Rosen, Bruce J. Baum
Journal: Molecular Therapy (2005)

Top of pageAbstract
Sj|[ouml]|gren's syndrome (SS) is an autoimmune disease characterized by a focal and diffuse lymphoid cell infiltration into the salivary and lacrimal glands. This chronic immune cell activation leads to reduced secretory function with symptoms of xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). It has been hypothesized that these sequelae are due to apoptosis of the exocrine epithelial cells. Apoptosis can be induced by cytotoxic T-lymphocytes (CTLs), which contain the enzyme Granzyme B (GrB) in cytoplasmic granules. GrB initiates a caspase-independent apoptosis pathway and is inhibited by serine proteinase inhibitor 6 (SPI-6) in the mouse. In this study, we evaluated the effect of transgenic SPI-6 produced in salivary glands after gene transfer to non-obese diabetic (NOD) mice, which develop exocrine gland infiltrates and are a commonly used disease model for SS.

We constructed two serotype 2 rAAV vectors, rAAVSPI-6 and rAAVLacZ (encoding |[beta]|-galactosidase; vector control) using the CMV promoter. rAAVs (1010 particles/gland) were administered directly into both submandibular glands of 8-week old female NOD mice (n=8) via retroductal delivery. Salivary flow rates were determined before vector delivery and at time of sacrifice (16-weeks old). Serum glucose levels and weight were measured weekly and diabetic mice (serum glucose|[ge]|400 mg/dL) were treated with insulin. After sacrifice, submandibular glands were harvested and analyzed for inflammatory infiltrates (focus scores), as well as SPI-6 expression and cytokine profile [mouse interleukins (IL)-2, 4, 6, 12, 18, interferon (IFN)-|[gamma]|, tumor necrosis factor-|[alpha]| and RANTES] in aqueous gland extracts.

At 8 weeks, salivary flow rates were not different between mice assigned to the rAAVSPI-6 and rAAVLacZ groups. In contrast, at 16 weeks flow rates were significantly higher in the rAAVSPI-6-treated mice (p=0.018). Submandibular gland IL-10 levels were significantly increased (p=0.009), while IFN-|[gamma]| levels were significantly decreased (p=0.029), in the rAAVSPI-6 mice compared to the rAAVLacZ group. There were no differences in focus scores, serum glucose levels or animal weights between the two treatment groups at 16 weeks.

Overall, these results suggest that SPI-6 gene transfer may be beneficial in limiting the autoimmune exocrinopathy of NOD mice.
Obstetric Myths versus Research Realities: A Guide to the Medical Literature
Authors: S. Oliver
Journal: BMJ (1995)

Henci Goer Bergin and Harvey, pp 385 ISBN 0 89789 242 9

In Obstetric Myths versus Research Realities Henci Goer attempts to steer readers through an “Alice in Wonderland world of obstetrics where you have to show that letting mothers walk around and choose positions of comfort is better than confining them to their backs in bed.” She discusses findings from research into maternity care in the context of women's lives, their physical and emotional well being, and their conversations with obstetricians and midwives. She is one …
Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study
Authors: MD Amylon, J Shuster, J Pullen, C Berard, MP Link, M Wharam, J Katz, A Yu, J Laver, Y Ravindranath, J Kurtzberg, S Desai, B Camitta, SB Murphy
Journal: Leukemia (1999)
Illness and Secrecy on the Supreme Court
Authors: Susan Okie
Journal: New England Journal of Medicine (2004)

Last October, soon after the opening of the current Supreme Court term, a lawyer who often argues cases before the Court noted with surprise that Chief Justice William Rehnquist was looking unusually pale and fragile as compared with his appearance six months previously. Some observers also noticed that Rehnquist's voice sounded hoarse. Before the month's end, while the Court was in recess, the 80-year-old chief justice was admitted to the National Naval Medical Center in Bethesda, Maryland, where — according to a terse official statement released by the Court — he underwent a tracheotomy “in connection with a recent diagnosis . . .
Incremental Prognostic Value of Rest-Redistribution <sup>201</sup> Tl Single-Photon Emission Computed Tomography
Authors: Tali Sharir, Daniel S. Berman, Howard C. Lewin, John D. Friedman, Ishac Cohen, Romalisa Miranda, Raluca D. Agafitei, Guido Germano
Journal: Circulation (1999)

The incremental prognostic value of rest-redistribution (201)Tl compared with stress and rest perfusion abnormalities has not been defined.We identified 458 patients who underwent rest (201)Tl /stress (exercise or adenosine) (99m)Tc sestamibi single-photon emission computed tomography (SPECT) and had late (18 to 24 hours) (201)Tl imaging, were not revascularized within 60 days of SPECT, and were followed up at >1 year. SPECT images were visually analyzed with the use of a 20-segment model on a scale of 0 to 4. Thirty-seven cardiac deaths (CDs) and 17 nonfatal myocardial infarctions occurred. Univariate Cox proportional hazards analysis showed that the presence of a large amount of rest (201)Tl reversibility (rest-late summed difference score [SDS] of >8) was a significant predictor of CD (chi(2) = 5.77, P = 0.02) and CD or myocardial infarction (chi(2) = 5.3, P = 0.02). The CD rate was 9.3% y(-1) in patients with rest-late SDS of >8 compared with 3.6% y(-1) in patients with a mild/moderate amount of rest reversibility (rest-late SDS 3 to 8) and 3.4% y(-1) in patients with no rest reversibility (rest-late SDS <3) (P = 0.029). Kaplan-Meier survival analysis demonstrated significantly lower cumulative survival rates in patients with rest-late SDS of >8 (P = 0.01). Multivariate Cox proportional hazards analysis demonstrated that the presence of a large amount of resting reversibility was an independent and incremental predictor of CD after adjustment for stress and rest perfusion information. Multivariate logistic regression analysis demonstrated that resting reversibility was not an independent predictor of referral to coronary angiography and revascularization.The identification of a large amount of resting (201)Tl reversibility is an independent predictor of CD over stress and rest perfusion abnormalities.
Molecular and functional studies of electrogenic Na+ transport in the distal colon and rectum of young and elderly subjects
Authors: E R Greig
Journal: Gut (2003)

<b>Background:</b> Human distal nephron and distal colon both exhibit mineralocorticoid sensitive electrogenic Na<sup>+</sup> absorption and make significant contributions to Na<sup>+</sup> homeostasis. Na<sup>+</sup> resorption in the distal nephron diminishes with age but it is unclear whether a similar change occurs in the distal colon. <b>Aims:</b> To evaluate the effect of age on expression of apical Na<sup>+</sup> channels and basolateral Na<sup>+</sup>, K<sup>+</sup>-ATPase, and on the responsiveness of electrogenic Na<sup>+</sup> absorption to mineralocorticoid stimulation in human distal colon and rectum. <b>Materials and methods:</b> Mucosal biopsies were obtained from healthy sigmoid colon and proximal rectum in “young” (aged 20–40 years) and “old” (aged 70 years or over) patients during routine colonoscopy/flexible sigmoidoscopy. Na<sup>+</sup> channel subunits and Na<sup>+</sup>, K<sup>+</sup>-ATPase isoforms were studied at the mRNA level by in situ hybridisation and northern blotting, and at the protein level by immunocytochemistry and western blotting. The mineralocorticoid responsiveness of electrogenic Na<sup>+</sup> absorption was evaluated in the two groups by measuring amiloride sensitive electrical potential difference (PD) in the proximal rectum before and 24 hours after oral administration of 1 mg of fludrocortisone. <b>Results:</b> Na<sup>+</sup> channel subunit and Na<sup>+</sup>, K<sup>+</sup>-ATPase isoform expression at the level of mRNA and protein was similar in “young” and “old” patients. Both basal and the fludrocortisone stimulated amiloride sensitive rectal PDs were similar in the two groups. <b>Conclusions:</b> In contrast with the distal nephron, mineralocorticoid sensitive electrogenic Na<sup>+</sup> absorption in the human distal colon does not diminish with age, and may be particularly important in maintaining Na<sup>+</sup> homeostasis in the elderly.
Chiropractic: A Profession at the Crossroads of Mainstream and Alternative Medicine
Authors: William C. Meeker, Scott Haldeman
Journal: Annals of Internal Medicine (2002)

Chiropractic is a large and well-established health care profession in the United States. In this overview, we briefly examine the development of chiropractic from humble and contentious beginnings to its current state at the crossroads of alternative and mainstream medicine. Chiropractic has taken on many of the attributes of an established profession, improving its educational and licensing systems and substantially increasing its market share in the past two decades. The public increasingly uses chiropractic largely for spinal pain syndromes and appears to be highly satisfied with the results. Of all the so-called alternative professions, chiropractic has made the largest inroads into private and public health care financing systems and is increasingly viewed as an effective specialty by many in the medical profession. Much of the positive evolution of chiropractic can be ascribed to a quarter century-long research effort focused on the core chiropractic procedure of spinal manipulation. This effort has helped bring spinal manipulation out of the investigational category to become one of the most studied forms of conservative treatment for spinal pain. Chiropractic theory is still controversial, but recent expansion in federal support of chiropractic research bodes well for further scientific development. The medical establishment has not yet fully accepted chiropractic as a mainstream form of care. The next decade should determine whether chiropractic maintains the trappings of an alternative health care profession or becomes fully integrated into all health care systems.
Hazards of Radiation Exposure for Pregnant Women
Authors: Harold M. Swartz
Journal: JAMA (1978)

CONCERN over the effects of radiation, especially in pregnant women, has increased along with the public concern over other potentially toxic factors in the environment. The emotional content of this concern is heightened in too many cases by physicians' ignorance of the subject. Here, as elsewhere in medicine, the key to reasonable public action is education on the real issues, and an essential starting point is the education of primary physicians. The goal of this article is to enable physicians to give confident, appropriate, convincing advice regarding radiation exposure of pregnant women. <h3>Levels of Radiation Pregnant Women May Receive</h3> Medical effects of radiation are dose dependent. The Table lists radiation doses for a number of common procedures. The dose that your patient receives may differ somewhat, depending on the conditions of the exposure, but in the absence of specific information the values in the Table provide an approximation. As will
Quality of Care for Older Patients With Cancer in the Veterans Health Administration Versus the Private Sector
Authors: Nancy L. Keating, Mary Beth Landrum, Elizabeth B. Lamont, Samuel R. Bozeman, Steven H. Krasnow, Lawrence N. Shulman, Jennifer R. Brown, Craig C. Earle, William K. Oh, Michael Rabin, Barbara J. McNeil
Journal: Annals of Internal Medicine (2011)

Background: The Veterans Health Administration (VHA) is the largest integrated health care system in the United States. Studies suggest that the VHA provides better preventive care and care for some chronic illnesses than does the private sector. Objective: To assess the quality of cancer care for older patients provided by the VHA versus fee-for-service Medicare. Design: Observational study of patients with cancer that was diagnosed between 2001 and 2004 who were followed through 2005. Setting: VHA and non-VHA hospitals and office-based practices. Patients: Men older than 65 years with incident colorectal, lung, or prostate cancer; lymphoma; or multiple myeloma. Measurements: Rates of processes of care for colorectal, lung, or prostate cancer; lymphoma; or multiple myeloma. Rates were adjusted by using propensity score weighting. Results: Compared with the fee-for-service Medicare population, the VHA population received diagnoses of colon (P < 0.001) and rectal (P = 0.007) cancer at earlier stages and had higher adjusted rates of curative surgery for colon cancer (92.7% vs. 90.5%; P < 0.010), standard chemotherapy for diffuse large B-cell non-Hodgkin lymphoma (71.1% vs. 59.3%; P < 0.001), and bisphosphonate therapy for multiple myeloma (62.1% vs. 50.4%; P < 0.001). The VHA population had lower adjusted rates of 3-dimensional conformal or intensity-modulated radiation therapy for prostate cancer treated with external-beam radiation therapy (61.6% vs. 86.0%; P < 0.001). Adjusted rates were similar for 9 other measures. Sensitivity analyses suggest that if patients with cancer in the VHA system have more severe comorbid illness than other patients, rates for most indicators would be higher in the VHA population than in the fee-for-service Medicare population. Limitation: This study included only older men and did not include information about performance status, severity of comorbid illness, or patient preferences. Conclusion: Care for older men with cancer in the VHA system was generally similar to or better than care for fee-for-service Medicare beneficiaries, although adoption of some expensive new technologies may be delayed in the VHA system. Primary Funding Source: Department of Veterans Affairs.
Passive smoking: Doubts about effectiveness of age adjustment
Authors: E. Milne
Journal: BMJ (2003)

Editor–According to Enstrom and Kabat's figures the greater had been a man's cigarette consumption in 1959 the less likely, it seems, was the death of his wife from coronary heart disease.1 However, an age bias existed in those women at the outset. In 1959 their mean age decreased with spousal smoking, such that the wives of men smoking 40 a …
Development and characterization of IL-21–producing CD4+ T cells
Authors: Akira Suto, Daisuke Kashiwakuma, Shin-ichiro Kagami, Koichi Hirose, Norihiko Watanabe, Kotaro Yokote, Yasushi Saito, Toshinori Nakayama, Michael J. Grusby, Itsuo Iwamoto, Hiroshi Nakajima
Journal: The Journal of Experimental Medicine (2008)

It has recently been shown that interleukin (IL)-21 is produced by Th17 cells, functions as an autocrine growth factor for Th17 cells, and plays critical roles in autoimmune diseases. In this study, we investigated the differentiation and characteristics of IL-21–producing CD4+ T cells by intracellular staining. Unexpectedly, we found that under Th17-polarizing conditions, the majority of IL-21–producing CD4+ T cells did not produce IL-17A and -17F. We also found that IL-6 and -21 potently induced the development of IL-21–producing CD4+ T cells without the induction of IL-4, IFN-γ, IL-17A, or IL-17F production. On the other hand, TGF-β inhibited IL-6– and IL-21–induced development of IL-21–producing CD4+ T cells. IL-2 enhanced the development of IL-21–producing CD4+ T cells under Th17-polarizing conditions. Finally, IL-21–producing CD4+ T cells exhibited a stable phenotype of IL-21 production in the presence of IL-6, but retained the potential to produce IL-4 under Th2-polarizing conditions and IL-17A under Th17-polarizing conditions. These results suggest that IL-21–producing CD4+ T cells exhibit distinct characteristics from Th17 cells and develop preferentially in an IL-6–rich environment devoid of TGF-β, and that IL-21 functions as an autocrine growth factor for IL-21–producing CD4+ T cells.
MSH2 deficient mice are viable and susceptible to lymphoid tumours
Authors: A.H. Reitmair, R. Schmits, A. Ewel, B. Bapat, M. Redston, A. Mitri, P. Waterhouse, H.-W Mittrücker, A. Wakeham, B. Liu, A. Thomason, H. Griesser, S. Gallinger, W.G. Ballhausen, R. Fishel, T. W. Mak
Journal: Nature Genetics (1995)
Radiographic Evidence of Silicosis Risk in the Diatomaceous Earth Industry
Authors: JANET M. HUGHES, HANS WEILL, HARVEY CHECKOWAY, ROBERT N. JONES, MELANIE M. HENRY, NICHOLAS J. HEYER, NOAH S. SEIXAS, PAUL A. DEMERS
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

There is limited and conflicting evidence regarding the exposure–response relationship between exposure to crystalline silica and silicosis; the level of risk to current workers remains uncertain. We conducted an epidemiologic investigation of 1,809 workers in the diatomaceous earth industry, where exposures to crystalline silica are primarily to the cristobalite form. On the basis of the median of three independent readings, 81 (4.5%) workers were judged to have opacities on chest radiographs (small opacities, profusion ⩾ 1/0, and/or large opacities). Age-adjusted relative risk of opacities increased significantly with cumulative exposure to crystalline silica. The concentration of respirable crystalline silica to which workers were exposed (highly correlated with period of hire) was an important determinant of risk after accounting for cumulative exposure. For workers with an average exposure to crystalline silica of ⩽ 0.50 mg/m3 (or hired ⩾ 1950), the cumulative risk of opacities for a cumulative exposure to crystalline silica of 2.0 mg/m3-yr was approximately 1.1%; for an average exposure > 0.50 mg/m3 (or hired < 1950), the corresponding cumulative risk was 3.7%. These findings indicate an exposure–response relationship between cumulative exposure to crystalline silica and radiographic opacities; moreover, the relationship was substantially steeper among workers exposed at the highest average concentrations of crystalline silica.
Rib lesions--two of a kind
Authors: E. H. Eliscu
Journal: JAMA (1969)

Dr. Raymond A. Berke: This 39-year-old white woman entered the hospital with a history of intermittent sharp pain in her back and side of eight months' duration. The pain was brought on by coughing or twisting and usually was relieved by the patient leaning forward. There was no history of trauma. Review of systems was not remarkable. Physical examination revealed a tender mass over the tenth rib posteriorly. The hematocrit reading was 34% and level of alkaline phosphatase, 7.1 Bodansky units. The results of all other laboratory examinations, including calcium, phosphorus, bilirubin, proteins, and bone marrow studies were normal. Chest roentgenograms were done at the time of admission.  Discussion  Dr. Laurence L. Robbins: Dr. New, can you see a lesion?  Dr. Paul F. J. New: Yes, there is quite a large osteolytic lesion in the posterior portion of the left tenth rib with an associated fracture (Fig 1). This is
Arise and Judge the Earth
Authors: Isaiah Kletenik
Journal: Annals of Internal Medicine (2012)

On Being a Doctor20 November 2012Arise and Judge the EarthIsaiah Kletenik, BAIsaiah Kletenik, BAFrom University of Washington School of Medicine, Seattle, WA 98195.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-10-201211200-00016 Audio Reading - “Arise and Judge the Earth” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Arise and Judge the Earth," by Isaiah Kletenik, BA. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Before medical school, I worked as a chaplain at the county hospital and regional trauma center. At the close of any encounter, I would offer to pray with the patient or the family members. I then asked a seemingly innocuous question: “How would you like to direct our prayers?” As with so many simple questions in medicine, I would be surprised at the power of what it revealed.I was awakened one morning from a fitful night of sleep in the humming cocoon of the hospital call room by a page. The nurse asked me to speak with a woman ... Author, Article, and Disclosure InformationAuthors: Isaiah Kletenik, BAAffiliations: From University of Washington School of Medicine, Seattle, WA 98195.Corresponding Author: Isaiah Kletenik, BA, University of Washington School of Medicine, Seattle, WA 98195; e-mail, [email protected]. PreviousarticleNextarticle Advertisement Audio Reading - “Arise and Judge the Earth” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Arise and Judge the Earth," by Isaiah Kletenik, BA. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 20 November 2012Volume 157, Issue 10Page: 752KeywordsBloodConsciousnessDeceptionNursesPediatric intensive care unitsPelvisSafetySleepThoraxTongue ePublished: 20 November 2012 Issue Published: 20 November 2012 Copyright & PermissionsCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Predisposition to Atherosclerosis
Authors: Kurt A. Oster
Journal: JAMA (1972)

<h3>To the Editor.—</h3> This letter is prompted by the Gordon and Kannel article, "Predisposition to Atherosclerosis in the Head, Heart, and Legs: The Framingham Study" (221:661, 1972). I must admire the skill, versatility, and endurance of the members of the National Heart and Lung Institute (NHLI)-sponsored Framingham group in reshuffling and rearranging the fixed set of data provided by their 16-year study of 5,209 adults. Like gambits on a chessboard of statistical analysis, the fragmentary pieces of information are moved according to the rules of regressive equations, which become more complicated with time. Which physician is not awed by the mysterious and impressive-looking formula <h3>[ΣβiSi/ViSi2]/[Σ1/ViSi2]</h3> which now supersedes the equally cabalistic equations of 1962<sup>1</sup>and 1967?<sup>2</sup>Should the reader-physician be at a loss to identify it, this formula was developed in 1967 by Walker and
HEADACHE AND EYESTRAIN.
Authors: GEORGE M. GOULD
Journal: JAMA (1906)

That a vast majority of all cases of headache, certainly nine-tenths, are due to eyestrain is a truth beyond question. That with headache, and often without it, a large indefinite proportion of digestional, nervous and psychic disease is due to the same cause is quite as true. A few cases may be due to malfunction or organic disease of other organs, but it is not known in how many of these cases eyestrain is the primary cause of these extraocular diseases; it is also unknown in how many the eyestrain may be the direct and contributing cause of the headache ascribed to the extraocular disease. <h3>PROFESSIONAL NARCOTISM.</h3> In 31 years the members of the American Ophthalmological Society have contributed three papers suggesting that eyestrain is the cause of some headache, and one member has contended that nasal disease, not eyestrain, is the cause of frontal headache. But there have been