tbuckley/cabot-search huggingface dataset:
Adult combined GH, prolactin, and TSH deficiency associated with circulating PIT-1 antibody in humans
Authors: Masaaki Yamamoto, Genzo Iguchi, Ryoko Takeno, Yasuhiko Okimura, Toshiaki Sano, Michiko Takahashi, Hitoshi Nishizawa, Anastasia Evi Handayaningshi, Hidenori Fukuoka, Maya Tobita, Takatoshi Saitoh, Katsuyoshi Tojo, Atsuko Mokubo, Akio Morinobu, Keiji Iida, Hidesuke Kaji, Susumu Seino, Kazuo Chihara, Yutaka Takahashi
Journal: Journal of Clinical Investigation (2010)

The pituitary-specific transcriptional factor-1 (PIT-1, also known as POU1F1), is an essential factor for multiple hormone-secreting cell types. A genetic defect in the PIT-1 gene results in congenital growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) deficiency. Here, we investigated 3 cases of adult-onset combined GH, PRL, and TSH deficiencies and found that the endocrinological phenotype in each was linked to autoimmunity directed against the PIT-1 protein. We detected anti-PIT-1 antibody along with various autoantibodies in the patients' sera. An ELISA-based screening revealed that this antibody was highly specific to the disease and absent in control subjects. Immunohistochemical analysis revealed that PIT-1-, GH-, PRL-, and TSH-positive cells were absent in the pituitary of patient 2, who also had a range of autoimmune endocrinopathies. These clinical manifestations were compatible with the definition of autoimmune polyendocrine syndrome (APS). However, the main manifestations of APS-I--hypoparathyroidism and Candida infection--were not observed and the pituitary abnormalities were obviously different from the hypophysitis associated with APS. These data suggest that these patients define a unique "anti-PIT-1 antibody syndrome," related to APS.
Sex Differences in Cardiac Arrest Survivors
Authors: Christine M. Albert, Brian A. McGovern, John B. Newell, Jeremy N. Ruskin
Journal: Circulation (1996)

Important sex differences in the epidemiology of sudden death and in the results of electrophysiological testing in survivors of cardiac arrest have been identified. These differences are currently poorly understood.Three hundred fifty-five consecutive survivors of out-of-hospital cardiac arrest (84 women and 271 men) referred for electrophysiologically guided therapy were analyzed retrospectively for sex differences in underlying pathology and predictors of outcome. Women were significantly less likely to have underlying coronary artery disease than men (45% versus 80%) and more likely to have other forms of heart disease or structurally normal hearts (P<.0001). The mean left ventricular ejection fraction was higher in women (0.46+/-0.18 versus 0.41+/-0.18, P<.05), and women were more likely to have no inducible arrhythmia at baseline electrophysiological testing (46% versus 27%, P=.002), although when the patients were stratified by coronary artery disease status, these sex differences were no longer present. The independent predictors of outcome differed between men and women. In men, a left ventricular ejection fraction of <0.40 was the most powerful independent predictor of total (relative risk, 2.8; 95% CI, 1.6 to 5.0; P<.0001) and cardiac (relative risk, 6.3; 95% CI, 2.9 to 13.5; P<.0001) mortality. In contrast, the presence of coronary artery disease was the only independent predictor of total (relative risk, 4.5; 95% CI, 1.5 to 13.4; P=.003) and cardiac (relative risk, 4.4; 95% CI, 1.2 to 15.6; P=.012) mortality in women.Females survivors of cardiac arrest are less likely to have underlying coronary artery disease. The predictors of total and cardiac mortality differ between male and female survivors. Coronary artery disease status is the most important predictor in women, and impaired left ventricular function is the most important predictor in men.
Retrosternal Dislocation of the Clavicle
Authors: George L. Lucas
Journal: JAMA (1965)

THE STERNOCLAVICULAR JOINT, which is essentially a universal joint with limited excursion, is the only articulation between the shoulder girdle and the trunk. Although the ligamentous and capsular attachments about the joint are well developed, the joint is not inherently stable due to the large sternal head of the clavicle which has its articulation with a smaller and oblique articular facet on the manubrium and adjacent portion of the first costal cartilage. Despite its apparently vulnerable position, injury to the sternoclavicular joint is not common, as evidenced by the figures of Rowe, who found only ten sternoclavicular joint injuries in 1,603 shoulder-girdle injuries at the Massachusetts General Hospital.<sup>1</sup> Three types of dislocation may occur at the sternoclavicular joint: most commonly, presternal; occasionally, suprasternal; and rarely, retrosternal. The latter, which is potentially the most dangerous, was encountered in only one of the ten sternoclavicular joint injuries reported by Rowe.<sup>1</sup>
Book Review Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management Edited by Martin H. Steinberg, Bernard G. Forget, Douglas R. Higgs, and Ronald L. Nagel. 1266 pp., illustrated. New York, Cambridge University Press, 2001. $275. 0-521-63266-8
Authors: David G. Nathan
Journal: New England Journal of Medicine (2001)
Cell culture-produced hepatitis C virus impairs plasmacytoid dendritic cell function
Authors: Masaaki Shiina, Barbara Rehermann
Journal: Hepatology (2007)

Previous studies suggested a functional impairment of dendritic cells (DCs) in patients with chronic hepatitis C. To investigate whether this effect was mediated by a direct interaction of hepatitis C virus (HCV) with DCs, we studied the effects of infectious cell culture-produced hepatitis C virus (HCVcc) on peripheral blood mononuclear cells (PBMCs), ex vivo isolated plasmacytoid, and myeloid DCs and in vitro generated monocyte-derived DCs of healthy blood donors. HCVcc inhibited toll-like receptor (TLR)-9 (CpG and herpes simples virus)-mediated interferon alpha (IFN-alpha) production by peripheral blood mononuclear cells (PBMC) and plasmacytoid DCs. This inhibitory effect was also observed in response to ultraviolet (UV)-inactivated, noninfectious HCVcc, and it was not abrogated by neutralizing antibodies, and thus did not appear to require DC infection. Influenza A virus restored maturation and TLR9-mediated IFN-alpha production. In contrast to its effect on plasmacytoid DCs, HCVcc did not inhibit TLR3-mediated and TLR4-mediated maturation and interleukin (IL)-12, IL-6, IL-10, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) production by myeloid DCs and monocyte-derived DCs. Likewise, HCVcc did neither alter the capacity of myeloid DCs nor monocyte-derived DCs to induce CD4 T cell proliferation. Whereas phagocytosis of apoptotic hepatoma cells resulted in DC maturation, this effect was independent of whether the phagocytosed Huh7.5.1 cells were infected with HCVcc. In contrast to HCVcc, vaccinia virus inhibited maturation and TNF-alpha expression of myeloid DC as well as maturation and IL-6 and IL-10 production of monocyte-derived DC.HCVcc inhibited plasmacytoid DCs but not myeloid-derived and monocytoid-derived DCs via a direct interaction that did not require infection. The response of plasmacytoid DCs to influenza A virus infection was not impaired.
Royal Brompton is accused of putting "a spanner in the works" of reorganising children's heart services by premature legal action
Authors: C. Dyer
Journal: BMJ (2012)

The Royal Brompton Hospital in London was accused this week of “putting a spanner in the works” of a much needed reorganisation of children’s heart services in England by launching legal action prematurely.

The claim came as the battle over proposals to close the children’s heart surgery unit at the Royal Brompton as part of a plan to concentrate services in fewer centres doing more operations reached the Court of Appeal in London.

As part of a nationwide exercise, the NHS’s Joint Committee of Primary Care Trusts …
Myocardial viability assessment by endocardial electroanatomic mapping: comparison with metabolic imaging and functional recovery after coronary revascularization
Authors: Karl-Christian Koch, Juergen vom Dahl, Monika Wenderdel, Bernd Nowak, Wolfgang M Schaefer, Alexander Sasse, Christoph Stellbrink, Udalrich Buell, Peter Hanrath
Journal: Journal of the American College of Cardiology (2001)
Giant Parathyroid Adenoma Demonstrated by Dual Tracer Parathyroid Imaging
Authors: CHARLES INTENZO, CAROL BERTOLI, CHAN H. PARK
Journal: Clinical Nuclear Medicine (1985)

Noninvasive diagnostic imaging modalities have played an increasingly important role in preoperative localization of parathyroid lesions. The radionuclide method using Tl-201 and Tc-99m subtraction imaging is quite successful in detecting such lesions, with a reported sensitivity of 92%. A case of surgically proven primary hyperparathyroidism, caused by an unusually large parathyroid adenoma and detected by the dual tracer method, is presented.
The "Inverted Pyramid of Accumulated Honors."
Authors: W. Gaston McFadden
Journal: JAMA (1898)

Shelbyville, Ind., April 39,1898. <h3>To the Editor:</h3> —I do not wish to be hypercritical, nor to be considered an<i>old fogy</i>, but I have often been painfully impressed with the thought that perhaps too many of the valuable papers in theJournalare over-burdened with the various titles and honors that have from time to time been conferred on the author. When I read an article in a medical journal I like to know the name of the writer, especially if there is anything new or original in it, but I confess it makes me<i>tired</i>to see a long list of colleges and hospitals he may have performed brief service in, as well as the various societies into whose<i>not exclusive</i>halls he has been admitted, hanging like an excrescence to his ethical title of M.D., in the shape and size of a huge Abracadabra.
Epidemiology and natural history of primary biliary cirrhosis in a Canadian health region: A population-based study
Authors: Robert P. Myers, Abdel Aziz M. Shaheen, Andrew Fong, Kelly W. Burak, Alex Wan, Mark G. Swain, Robert J. Hilsden, Lloyd Sutherland, Hude Quan
Journal: Hepatology (2009)

The recent epidemiology and outcomes of primary biliary cirrhosis (PBC) in North America are incompletely described, partly due to difficulties in case ascertainment. In light of their availability, broad coverage, and limited expense, administrative databases may facilitate such investigations. We used population-based administrative data (inpatient, ambulatory care, and physician billing databases) and a validated International Classification of Diseases coding algorithm to describe the epidemiology and natural history of PBC in the Calgary Health Region (population approximately 1.1 million). Between 1996 and 2002, the overall age/sex-adjusted annual incidence of PBC was 30.3 cases per million (48.4 per million in women, 10.4 per million in men). Although the incidence remained stable, the prevalence increased from 100 per million in 1996 to 227 per million in 2002 (P < 0.0005). Among 137 incident cases with a total follow-up of 801 person-years from diagnosis (median 5.8 years), 27 patients (20%) died and six (4.4%) underwent liver transplantation. The estimated 10-year probabilities of survival, liver transplantation, and transplant-free survival were 73% (95% confidence interval [CI] 60%-83%), 6% (95% CI 2.5%-12.6%), and 68% (95% CI 55%-78%), respectively. Survival in PBC patients was significantly lower than that of the age/sex-matched Canadian population (standardized mortality ratio 2.87; 95% CI 1.89-4.17); male sex (hazard ratio [HR] 3.80; 95% CI 1.85-7.82) and an older age at diagnosis (HR per additional year, 1.06; 95% CI 1.03-1.10) were independent predictors of mortality.This population-based study demonstrates that the burden of PBC in Canada is high and growing. Survival of PBC patients is significantly lower than that of the general population, emphasizing the importance of developing new therapies for this condition.
Letter: Potentiation of tardive dyskinesia: possible drug interaction.
Authors: P F Marriett
Journal: BMJ (1975)

2 19 F. 5 Genital herpes (persisting for H.S.V. isolated from genital lesions.Fourfold 16 days) C.F. antibody rise to H.S.V. 66 34 62 3 5 M. 20 Erythema multiforme Primary H.S.V. infection.Sibling with herpes labialis.72 38 100 4 68 F. N.K. Atypical purpuric varicelliform Carcinoma of cervix.Treated with rash cyclophosphamide 2 months previously; on steroids.>4-fold C.F. antibody
Cutaneous reactions to recombinant human interferon beta-1b: The clinical and histologic spectrum
Authors: George W. Elgart, William Sheremata, Yeon S. Ahn
Journal: Journal of the American Academy of Dermatology (1997)

Background: Recombinant human interferon beta-1b has been recently approved for the treatment of multiple sclerosis. A significant proportion of patients treated with this medication experienced cutaneous reactions. Objective: We describe the clinical and histologic features of cutaneous reactions to recombinant human interferon beta-1b. Methods: Consecutive patients with cutaneous reactions to recombinant interferon beta-1b were evaluated clinically and by biopsy. Results: Clinical lesions varied from subtle uninflamed sclerotic dermal plaques to erythematous plaques to cutaneous ulcers at injection sites. The nonsclerotic lesions were frequently painful. The firm plaques showed fibrosis histologically, whereas nonsclerotic inflammatory lesions demonstrated a consistent pattern of vascular thrombosis. Hematologic evaluation demonstrated platelet activation in most patients with inflammatory lesions, a feature also noted before interferon treatment in some patients. Conclusion: Therapy with recombinant interferon beta-1b is associated with a spectrum of cutaneous reactions and vascular thrombosis. (J Am Acad Dermatol 1997;37:553-8.)
Abstract ES7-2: Tumor Dormancy from an Experimental Biologist's Perspective
Authors: AF Chambers
Journal: Cancer Research (2012)

Abstract Survival from breast cancer has improved steadily over the past decades. However, most breast cancer deaths are due to metastasis, and considerably less progress has been made against metastatic disease. We still know remarkably little about preventing or delaying metastatic recurrence or effectively treating the cancer if it does recur. Making breast cancer treatment even more challenging is the fact that breast cancer patients may appear to be cured of their disease, only to have it return later. These recurrences can happen even decades after apparently successful primary treatment. This creates years of uncertainty for breast cancer patients, who do not know if they have been cured or if the cancer will return, and makes clinical management difficult. We have used experimental models, both in vitro and in vivo, to try to understand the process of breast cancer metastasis. We have found that a population of cancer cells can remain as dormant cells, and have shown that these cells can resist being killed by cytotoxic chemotherapy that successfully kills actively diving cells. Experimental studies raise questions that must be addressed clinically. For example, what is the prevalence of dormant cells in breast cancer patients – are they common or rare? Are there factors inherent to the cancer cells that influence the likelihood of dormant cells persisting and subsequently re-awakening? Conversely, are there host microenvironmental factors, such as diet, exercise or stress, that can influence whether dormant cells persist and re-awaken? This information will be important in learning better how to prevent, delay and treat metastatic breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES7-2.
Prostate-Specific Antigen Progression Predicts Overall Survival in Patients With Metastatic Prostate Cancer: Data from Southwest Oncology Group Trials 9346 (Intergroup Study 0162) and 9916
Authors: Maha Hussain, Bryan Goldman, Cathy Tangen, Celestia S. Higano, Daniel P. Petrylak, George Wilding, Atif M. Akdas, Eric J. Small, Bryan J. Donnelly, Subramanian Kanaga Sundram, Patrick A. Burch, Robert S. DiPaola, E. David Crawford
Journal: Journal of Clinical Oncology (2009)

Prostate-specific antigen progression (PSA-P) is an indicator of progression in hormone-sensitive (HS) and castration-resistant (CR) prostate cancer (PC). We evaluated different definitions of PSA-P as predictors of overall survival (OS).A total of 1,078 patients with HSPC who were on hormones (Southwest Oncology Group [SWOG] trial 9346 [S9346]) and 597 patients with CRPC who were treated with chemotherapy (SWOG trial 9916 [S9916]) were eligible for this analysis. PSA-P definitions tested included the following: PSA Working Group, Prostate Cancer Working Group (PCWG 2008), and other definitions. A time-varying approach analyzed associations between PSA-P at any time and OS. A landmark analysis examined the relationship between PSA-P status at 7 months for S9346, or 3 months for S9916, and subsequent OS.In the time-varying analysis, both working groups definitions were strongly associated with OS (P < .001) in both study settings. In patients enrolled onto S9346, both definitions predicted a 2.4-fold increased risk of death (ROD) and a greater than four-fold increased ROD if PSA-P occurred in the first 7 months. In S9916, they predicted a 40% increase in ROD and a two-fold increase in ROD if PSA-P occurred at 3 months. In landmark analyses of patients on S9346 by using the PCWG 2008 definition of PSA-P, median subsequent OS was 10 months versus 44 months in patients who did or did not have PSA-P by 7 months, respectively; in S9916, data were 11 months versus 18 months for patients who did or did not have PSA-P by 3 months, respectively.PSA-P, defined as an increase of > or = 25% greater than the nadir and an absolute increase of at least 2 or 5 ng/mL, predicts OS in HSPC and CRPC and may be a suitable end point for phase II studies in these settings.
Dependence of the Cytotoxicity of DNA-Damaging Agents on the Mismatch Repair Status of Human Cells
Authors: Efterpi Papouli, Petr Cejka, Josef Jiricny
Journal: Cancer Research (2004)

Mismatch repair (MMR) deficiency was reported to increase resistance of mammalian cells to killing by several genotoxic substances. However, although MMR-deficient cells are approximately 100-fold more resistant to killing by S(N)1 type methylating agents than MMR-proficient controls, the sensitivity differences reported for the other agents were typically <2-fold. To test whether these differences were linked to factors other than MMR status, we studied the cytotoxicities of mitomycin C, chloroethylcyclohexyl nitrosourea, melphalan, psoralen-UVA, etoposide, camptothecin, ionizing radiation, and cis-dichlorodiaminoplatinum (cisplatin) in a strictly isogenic system. We now report that MMR deficiency reproducibly desensitized cells solely to cisplatin.
Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies
Authors: Milan Tomana, Jan Novak, Bruce A. Julian, Karel Matousovic, Karel Konecny, Jiri Mestecky
Journal: Journal of Clinical Investigation (1999)

Circulating immune complexes (CICs) isolated from sera of patients with IgA nephropathy (IgAN) consist of undergalactosylated, mostly polymeric, and J chain–containing IgA1 and IgG antibodies specific for N-acetylgalactosamine (GalNAc) residues in O-linked glycans of the hinge region of IgA1 heavy chains. Antibodies with such specificity occur in sera of IgAN patients, and in smaller quantities in patients with non-IgA proliferative glomerulonephritis and in healthy controls; they are present mainly in the IgG (predominantly IgG2 subclass), and less frequently in the IgA1 isotype. Their specificity for GalNAc was determined by reactivity with IgA1 myeloma proteins with enzymatically removed N-acetylneuraminic acid (NeuNAc) and galactose (Gal); removal of the O-linked glycans of IgA1 resulted in significantly decreased reactivity. Furthermore, IgA2 proteins that lack the hinge region with O-linked glycans but are otherwise structurally similar to IgA1 did not react with IgG or IgA1 antibodies. The re-formation of isolated and acid-dissociated CICs was inhibited more effectively by IgA1 lacking NeuNAc and Gal than by intact IgA1. Immobilized GalNAc and asialo-ovine submaxillary mucin (rich in O-linked glycans) were also effective inhibitors. Our results suggest that the deficiency of Gal in the hinge region of IgA1 molecules results in the generation of antigenic determinants containing GalNAc residues that are recognized by naturally occurring IgG and IgA1 antibodies.
Septic Haemophilus influenzae Polyarthritis Demonstrated Best with Tc-99m HMPAO Labeled Leukocytes
Authors: MARTTI VORNE, SEPPO SALO, ILKKA ANTTOLAINEN, HEIKKI PELTOLA, RISTO MOKKA
Journal: Clinical Nuclear Medicine (1990)

A 5-year-old girl with fever and tenderness in her left wrist and right ankle was hospitalized. Bone scanning and Tc-99m labeled leukocyte imaging showed increased uptake in these joints and also in her left knee. These radionuclide methods helped determine the diagnosis and were superior to plain radiography and CT scanning. Uptake was greater on leukocyte imaging than it was on the bone scan. The patient had infectious polyarthritis caused by Haemophilus influenzae, which is a very rare cause of acute polyarthritis in children older than 2 years. The patient fully recovered with antibiotic therapy, and no surgical procedure was needed.
Quarantine Against Plague.
Authors: Albert S. Ashmead
Journal: JAMA (1901)

New York, March 8, 1901. <h3>To the Editor:</h3> —Dr. Doty is quoted by Dr. Bracken, inThe Journalof March 9, p. 677, as having said that "rats collected at New York, from coffee-carrying vessels from Rio Janeiro and Santos, during the recent outbreak of plague in those two places, were examined bacteriologically, and in no instance was there the slightest evidence of bubonic plague." I add that neither did Dr. Doty's bacteriological examination disclose bubonic plague in the body of the dead laborer on one of the lighters to which the cargo was being removed in mid-bay—who suddenly died of pneumonia. Yet the man's hands had been in direct contact with the rat-infected cargo, and had breathed into his lungs its dust. Credit is due President Murphy, of the New York Board of Health, for his firmness in not permitting the port quarantine service to unload those ships at
Segregation of agonist and antagonist systems minimizes the benefits of polarity
Authors: William A. MacKay
Journal: Behavioral and Brain Sciences (1997)

A purely kinematic theory of movement runs the risk of having no explanatory power because it neglects the internal generative structures of the central nervous system. Distributed interaction between the agonist and antagonist systems would better simulate physiological mechanisms of oscillation, lateral inhibition, and synchronization, all of which have important roles in motor control.
The benefits of aptitude testing for selecting medical students
Authors: Sandra Nicholson
Journal: BMJ (2005)

The A level is the most common tool for assessing school leavers applying for higher education, including medicine. If medical school outcome is accurately predicted by A level grades, as described by McManus et al,1 what place, if any, do aptitude tests have in the selection of medical students?

Applications for medical school from appropriately highly qualified candidates have increased year on year2 until it has become increasingly difficult to discriminate between candidates with similar A level performance. Most medical schools wish to select future doctors using non-cognitive attributes alongside A levels, but procedures, such as interviewing, are time consuming and labour intensive. An urgent need is to reduce the number of …