tbuckley/cabot-search huggingface dataset:
Abstract P2-11-15: Immunohistochemical assessment of Ki67 with the antibodies SP6 and MIB1 - A comparison of prognostic information and reproducibility
Authors: M Ekholm, S Beglerbegovic, D Grabau, K Lövgren, P Malmström, L Werner-Hartman, M Fernö
Journal: Cancer Research (2013)

Abstract Background Proliferation is a key feature in breast cancer and also a clinical important factor for prognosis and treatment prediction. In the St Gallen Consensus of 2011, immunohistochemically analysed Ki67 was adopted as a surrogate marker to distinguish the “luminal A” from the “luminal B” subtype, in order to select patients with estrogen receptor positive disease expected to benefit from adjuvant chemotherapy. The mouse monoclonal antibody MIB1 is the generally accepted antibody for assessment of Ki67. However, other antibodies have been developed, e.g. the rabbit monoclonal antibody SP6. The assessment of Ki67 with MIB1 is unfortunately associated with a considerable lack of reproducibility. Rabbit monoclonal antibodies generally tend to have higher specificity without loss of sensitivity, compared to corresponding mouse monoclonal antibodies. SP6 has also been found to have reduced background staining compared to MIB1. According to these advantages, SP6 may be an alternative to MIB1 for routine staining of Ki67. Any methodological modification should, according to international recommendations, be compared against a clinically validated assay and demonstrate acceptable concordance before being introduced in clinical routine. The analysis of Ki67 with SP6 therefore needs to be evaluated and compared to MIB1 in a cohort of breast cancer patients with clinical follow-up. Aims To compare the antibodies SP6 and MIB1 for immunohistochemical assessment of Ki67 in primary breast cancer regarding prognostic strength and reproducibility of the evaluation. Methods Tissue microarray from a cohort of 237 premenopausal women with node-negative breast cancer was used for assessment of Ki67, with both SP6 and MIB1, by three different investigators. The 7th decile was applied for defining cut-off. Distant disease-free survival (DDFS) was used as endpoint and the follow-up was restricted to 5 years. Results Ninety per cent of the samples were classified into the same group, either high or low Ki67, irrespective of antibody used. Ki67 (high vs. low), analysed with both antibodies was associated to DDFS (34 events) in the univariable analyses (SP6: HR 2.6, 95% CI 1.3-5.2, p = 0.01 and MIB1: HR 2.8, 95% CI 1.4-5.7 p = 0.004) and showed borderline significance for DDFS in the multivariable analyses, also including HER2, age, and tumour size (SP6: HR 2.0, 95% CI 0.93-4.5, p = 0.074 and MIB1: HR 2.2, 95% CI 0.97-4.8, p = 0.058). The agreement between different assessors was somewhat higher for MIB1 than for SP6 (kappa-values 0.83-0.88 vs. 0.72-0.77). Conclusions SP6 was not superior to MIB1 and the two antibodies were comparable in the assessment of Ki67 for prognostic considerations in primary breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-15.
EPIDEMIC MENINGITIS IN THE FIRST THREE MONTHS OF LIFE
Authors: JOSEPHINE B. NEAL
Journal: JAMA (1927)

The literature on epidemic meningitis in infancy is meager. Studies of meningitis in early infancy with reviews of the literature have been made by Barron,<sup>1</sup>Root,<sup>2</sup>and Cooke and Bell,<sup>3</sup>and an interesting case of epidemic meningitis has been recently reported by Sturtevant.<sup>4</sup>In view of the undoubted fact that a considerable number of cases are never reported, it does not seem important to make a very careful study of the literature with an attempt to collect the number of cases. It appears to be a general belief that all forms of meningitis are rare in early infancy. Barron<sup>1</sup>writes, "Although meningitis is a disease quite common in childhood, it is one that is extremely rare during the early months of infancy." Sturtevant<sup>4</sup>states: "Meningococcus meningitis is an extremely rare disease in early infancy." Similar statements are made by Root<sup>2</sup>and by Cooke
Trusts should cut workload of senior physicians to retain them
Authors: Brettingham Madeleine
Journal: BMJ (2005)

More than three quarters of consultant physicians currently in post intend to retire early. This exodus could leave every large hospital in the United Kingdom short of two physicians and could mean a loss of over 6000 working years in total to the NHS, the Federation of Royal Colleges of Physicians has warned.

The findings, from the federation's 2004 annual census of UK consultant physicians, indicate that the government needs to take more account of changing working patterns. Doctors are leaving the profession early, escaping long working hours and stressful conditions, says the federation, which comprises the Royal Colleges of Physicians in London, Edinburgh, and …
Intravenous Esomeprazole for Prevention of Recurrent Peptic Ulcer Bleeding
Authors: Joseph J.Y. Sung
Journal: Annals of Internal Medicine (2009)

Background: Use of proton-pump inhibitors in the management of peptic ulcer bleeding is controversial because discrepant results have been reported in different ethnic groups. Objective: To determine whether intravenous esomeprazole prevents recurrent peptic ulcer bleeding better than placebo in a multiethnic patient sample. Design: Randomized trial conducted between October 2005 and December 2007; patients, providers, and researchers were blinded to group assignment. Setting: 91 hospital emergency departments in 16 countries. Patients: Patients 18 years or older with peptic ulcer bleeding from a single gastric or duodenal ulcer showing high-risk stigmata. Intervention: Intravenous esomeprazole bolus, 80 mg, followed by 8-mg/h infusion, over 72 hours or matching placebo, each given after successful endoscopic hemostasis. Intervention was allocated by computer-generated randomization. After infusion, both groups received oral esomeprazole, 40 mg/d, for 27 days. Measurements: The primary end point was rate of clinically significant recurrent bleeding within 72 hours. Recurrent bleeding within 7 and 30 days, death, surgery, endoscopic re-treatment, blood transfusions, hospitalization, and safety were also assessed. Results: Of 767 patients randomly assigned, 764 provided data for an intention-to-treat analysis (375 esomeprazole recipients and 389 placebo recipients). Fewer patients receiving intravenous esomeprazole (22 of 375) had recurrent bleeding within 72 hours than those receiving placebo (40 of 389) (5.9% vs. 10.3%; difference, 4.4 percentage points [95% CI, 0.6% to 8.3%]; P = 0.026). The difference in bleeding recurrence remained significant at 7 days and 30 days (P = 0.010). Esomeprazole also reduced endoscopic re-treatment (6.4% vs. 11.6%; difference, 5.2 percentage points [95% CI of difference, 1.1 percentage points to 9.2 percentage points]; P = 0.012), surgery (2.7% vs. 5.4%), and all-cause mortality rates (0.8% vs. 2.1%) more than placebo, although differences for the latter 2 comparisons were not significant. About 10% and 40% of patients in both groups reported serious and nonserious adverse events, respectively. Limitation: Endoscopic therapy was not completely standardized; some patients received epinephrine injection, thermal coagulation, or hemoclips alone, whereas others received combination therapy, but there were similar proportions with single therapy in each group. Conclusion: High-dose intravenous esomeprazole given after successful endoscopic therapy to patients with high-risk peptic ulcer bleeding reduced recurrent bleeding at 72 hours and had sustained clinical benefits for up to 30 days. Primary Funding Source: AstraZeneca Research and Development.
Seminars in Medical Ethics and Medical Humanism
Authors: Lester S. King
Journal: JAMA (1974)

The great scientific advances and the increased ability to deal with disease raise social problems undreamed of a half century ago. The relations of medicine to society—the socalled sociology of medicine—is now recognized as a major challenge in medical education and practice. Sociology of medicine is a poorly defined concept, for it merges with numerous other fields—economics, political philosophy, practical politics (a very different thing); it relates to humanistic subjects like ethics and history, literature and art, and the nature and development of culture. These subjects are not merely abstract topics, for the economic, cultural, and ethical problems to which they give rise are becoming more and more intrusive and are demanding answers. We can be absolutely certain that answers will be forthcoming, hammered out by irresistible pressures.  There is growing realization that physicians must be equipped to play a part in the process that will eventually find suitable answers.
Red blood cell transfusion in non-bleeding critically ill patients with moderate anemia: is there a benefit?
Authors: Santiago R. Leal-Noval, Manuel Muñoz-Gómez, Mercedes Jiménez-Sánchez, Aurelio Cayuela, María Leal-Romero, Antonio Puppo-Moreno, Judy Enamorado, Victoria Arellano-Orden
Journal: Intensive Care Medicine (2012)
Effects of altered prenatal hormonal environment on expression of autoimmune disease in NZB/NZW mice.
Authors: S E Walker, L W Keisler, C W Caldwell, A B Kier, F S vom Saal
Journal: Environmental Health Perspectives (1996)

F1 hybrid New Zealand Black (NZB) x New Zealand White (NZM) (NZB/NZW) mice spontaneously develop an autoimmune disease analogous to systemic lupus erythematosus (SLE). Testosterone experts a powerful suppressive effect on this disorder in adult NZB/NZW mice. A series of experiments was designed to determine if disease would also be suppressed by exposing fetal NZB/NZW mice to increased testosterone. A model was developed in which NZB dams carrying NZB/NZW fetuses were treated with testosterone in a dose adequate to masculinize the external genitalia in female fetuses. NZB/NZW mice that were derived from testosterone-treated dams and control NZB/NZW offspring were followed in a longevity study and had serial assays to assess development of SLE. Additional experiments were carried out to measure lymphocyte subsets and responses to mitogens. Results were compared with F1 hybrid offspring of C57BL/6 dams crossed with DBA/2 males, which are not autoimmune and do not develop SLE. Spleen cells from these groups were tested for Thy 1.2, CD4, CD8, and IgM receptors, and for responses to the mitogens Concanavalin A (ConA) and lipopolysaccharide. Control male NZB/NZW fetuses had unexpectedly high serum estradiol, which decreased significantly with maternal testosterone treatment. The testosterone-exposed male NZB/NZW fetuses developed into adults that lived longer than male NZB/NZW controls. Testosterone treatment of the dam was associated with elevated terminal anti-DNA levels but did not alter markers of renal diseases in adult NZB/NZW mice of either sex. Testosterone-exposed NZB/NZW females had altered T-lymphocyte subsets and testosterone-exposed males had increased response to ConA compared to controls. In male NZB/NZW fetuses whose mothers were administered testosterone, the naturally high level of circulating estradiol observed in untreated male fetuses was decreased significantly. This decrease was associated with an increase in longevity. This unique observation has important implications for fetal exposure to endocrine disruptors in the environment.
Apparent Transmission of Human T-Cell Leukemia Virus Type III to a Heterosexual Woman with the Acquired Immunodeficiency Syndrome
Authors: JEROME E. GROOPMAN
Journal: Annals of Internal Medicine (1985)

A 24-year-old woman developed the acquired immunodeficiency syndrome with lymphadenopathy, oral candidiasis, and Kaposi's sarcoma. Her only known risk factor for the syndrome was sexual contact with an asymptomatic Haitian man. The woman had serologic evidence for infection with human T-cell lymphotropic virus type III, and this virus was recovered from the saliva of her sexual partner. Epidemiologic and virologic studies of the cases of such patients provide further evidence of a primary pathogenetic role for this retrovirus in the acquired immunodeficiency syndrome.
Remarks on the Subcutaneous Division of the Neck of the Thigh-Bone, as Compared with Other Operations for Rectifying Extreme Distortion at the Hip-Joint, with Bony Anchylosis
Authors: W. Adams
Journal: BMJ (1870)

CASES of extreme deformity at the hip-joint, with the thigh flexed upon the pelvis, arid generally adducted or drawn towards the opposite limb, sometimes even crossing over the opposite limb, are not uncommonly met with in surgical practice as the result of various forms of hip-joint in- flammation.Anchylosis of the hip-joint may be either true or false as in other articulations.By true anchylosis, I mean bony union of the articular surfaces after complete destruction of the joint; and by false anchylosis,
126. The Formation of Stable and Mature Blood Vessels Requires the Proper Timing of VEGF Expression
Authors: Sabrina Tafuro, Serena Zacchigna, Lorena Zentilin, Marina Dapas, Mauro Giacca
Journal: Molecular Therapy (2005)

The delivery of pro-angiogenic factors via gene transfer has been demonstrated to induce favorable effects in the revascularization of ischemic tissues. In this respect, AAV vectors represent outstanding tools for cardiovascular gene transfer given their specific tropism for skeletal and cardiac muscle cells and the prolonged expression of their transgenes. We have previously observed that the injection of AAV-VEGF in the mouse skeletal muscle determines a marked neo-vascularization response, starting at a few weeks after treatment and persisting for several months.
Comment on: Jeon et al. <i>Helicobacter pylori</i> Infection Is Associated With an Increased Rate of Diabetes. Diabetes Care 2012;35:520–525
Authors: Stergios A. Polyzos, Jannis Kountouras, Christos Zavos, Georgia Deretzi
Journal: Diabetes Care (2012)

Jeon et al. (1) stated that infectious agents might have an impact on cardiovascular disease (CVD) and metabolic syndrome, potentially mediated by increased inflammatory markers, including C-reactive protein (CRP) and interleukin (IL)-6. However, epidemiological studies investigating the impact of pathogen burden on diabetes have been limited; cross-sectional studies examining systemic pathogens and insulin resistance (IR) or prevalent diabetes have produced equivocal findings, and Helicobacter pylori infection ( Hp -I) shows no association with IR or prevalent diabetes.

We previously conducted a systematic review summarizing the epidemiological evidence regarding the association between Hp -I and IR quantitative-only indices (2). A positive association between Hp -I and homeostasis model assessment of insulin resistance …
The effect of topical tretinoin on photodamaged facial skin; the Thai experience
Authors: R. KOTRAJARAS, A.M. KLIGMAN
Journal: British Journal of Dermatology (1993)

Because of the climate in Bangkok, Thailand, a prematurely aged appearance is common in adults beyond 40 years of age. Sixty-one Thai people with moderate to severe signs of dermatoheliosis applied 0.05% tretinoin cream to the face once daily for 6-12 months. Four-mm punch biopsies were obtained from the cheeks before and after treatment. These were formalin-fixed and evaluated histochemically. A surprising degree of photodamage was noted histologically in these dark-skinned people. After 6 months of tretinoin, epidermal atypia and atrophy were largely corrected. There was a great diminution in the density of melanin granules within keratinocytes and corneocytes. Tretinoin did not significantly affect the dermal matrix after 6 months. However, after 12 months, a thin band of new collagen was deposited beneath the epidermis, accompanied by the formation of new vessels (angiogenesis). By global assessment, after 12 months most subjects experienced at least moderate improvement in appearance, especially with regard to hyperpigmented spots and fine wrinkles.
Are Midwives to be Abolished or Bettered?
Authors: J. H. Aveling
Journal: BMJ (1890)

Among the military population continued fevers have always been very common-much more so formerly than now.At one time the troops suffered so much from continued fevers that nearly half of the total number of deaths was caused by them.Dr. Parkes states that in the ten years 1837 to 1846 there were 1,004 cases of continued fever out of 11,224 men, or 88 per 1,000 of strength; while in 1859 there were only 11 cases out of 1,074 men.Many of these were unquestionably enteric fever; a large number
Reduced Mortality Risk in Alcoholics Who Achieve Long-term Abstinence
Authors: Kim D. Bullock
Journal: JAMA (1992)

<h3>Objectives.</h3> —To determine if alcoholic men who achieved stable abstinence experienced fewer deaths than those who relapsed and to develop a model predictive of premature mortality. <h3>Design.</h3> —A cohort of alcoholic men recruited into a prospective study of neurocognitive effects of alcoholism was followed up from 1 through 11 years. A demographically equated group of nonalcoholic men was also followed up. Alcoholics were classified as stable abstainers or relapsers. <h3>Setting.</h3> —Alcoholics were patients or ex-patients from a Department of Veterans Affairs Alcoholism Treatment Program and/or members of local chapters of Alcoholics Anonymous. <h3>Participants.</h3> —There were 234 alcoholic men who met the<i>Diagnostic and Statistical Manual of Mental Disorders, Third Edition</i>, criteria for alcohol dependence. Follow-up status regarding relapse and mortality was obtained for 199 alcoholic subjects (85%). Of these, 101 had relapsed and 98 had abstained. Ninety-eight nonalcoholic controls equated for age, education, and sex also participated. Mortality status was obtained for 92 subjects in this group (94%). <h3>Exclusions.</h3> —Major medical and psychiatric illness and history of nonalcoholic drug abuse. <h3>Main Outcome Measure.</h3> —Death during a follow-up period of 1 through 11 years. Death was ascertained through the National Death Index, the California State Department of Health and Vital Statistics, the State Department of Motor Vehicles, and through personal contact with informants, relatives, and significant others of the subjects. <h3>Results.</h3> —There were 19 deaths among relapsed alcoholics compared with the expected number of 3.83 (99% confidence interval (CI), 9.64 to 33.38). Among abstinent alcoholics there were four deaths (expected = 3.21; 99% Cl, 0.67 to 12.59). The standardized mortality ratio for relapsed alcoholics was 4.96, which significantly exceeded the expected ratio (<i>P</i>&lt;.001), whereas the standardized mortality ratio for abstinent alcoholics (1.25) was indistinguishable from the expected. Cox proportional hazards analysis was used to determine if any of several demographic, medical, cognitive, or drinking history variables (in addition to relapse) helped predict mortality among alcoholics. Only relapse was significantly related to increased mortality (χ<sup>2</sup>= 9.15,<i>P</i>=.003). <h3>Conclusions.</h3> —Alcoholic men who achieve stable abstinence do not differ from nonalcoholic men in mortality experience; however, alcoholics who relapse die at a rate 4.96 times that of an age-, sex-, and race-matched representative sample from the US Bureau of the Census. (<i>JAMA</i>. 1992;267:668-672)
Cost Sharing, Caps on Benefits, and the Chronically Ill — A Policy Mismatch
Authors: Kenneth E. Thorpe
Journal: New England Journal of Medicine (2006)

Crafting effective policy solutions to the high and rising costs of health care requires a clear understanding of the underlying problem. First, more than 75 percent of health care spending is traced back to patients with a chronic illness.1 Patients who are chronically ill have long-lasting conditions that, in general, require predictable medical interventions. Although these medical interventions are well established, chronically ill patients receive only 56 percent of the recommended care each year.2 Second, most of the increase in health care spending is associated with a rise in the prevalence of treated disease, much of which is in turn . . .
Fetal tissue can synthesize a placental hormone. Evidence for chorionic gonadotropin beta-subunit synthesis by human fetal kidney.
Authors: W G McGregor, W J Raymoure, R W Kuhn, R B Jaffe
Journal: Journal of Clinical Investigation (1981)

Metabolically active tissues from second trimester human fetuses were examined for their ability to synthesize the placental hormones chorionic gonadotropin and chorionic somatomammotropin. During short-term incubation studies both placenta and fetal kidney were found to synthesize and secrete the beta-subunit of chorionic gonadotropin, whereas its synthesis was not observed in fetal liver, lung or muscle. In addition, chorionic somatomammotropin synthesis and secretion was demonstrated with placental tissue but could not be detected in any of the fetal tissues examined. These observations constitute the first evidence that the genome of a fetal tissue directs the synthesis of what is considered a placental hormone.
Alteration of Digoxin Pharmacokinetics by a Single Dose of Quinidine
Authors: Tsan-Shih Chen
Journal: JAMA (1980)

To determine whether a single dose of quinidine sulfate might alter serum digoxin levels, patients receiving maintenance digoxin therapy who required quinidine had their serum digoxin levels measured after oral administration of digoxin, quinidine, or both. In group 1, digoxin and quinidine were administered orally together; in group 2, digoxin was administered orally alone; and in group 3, quinidine was administered orally, 24 hours after the last dose of digoxin. In group 1, serum digoxin level increased by 2.0+/-0.4 ng/mL (from 1.0+/-0.1 ng/mL), but in group 2, serum digoxin level increased by only 1.0+/-0.1 ng/mL (from 1.0+/-0.1 ng/mL). Group 3 showed no change in serum digoxin concentration. Time of maximum digoxin concentration also occurred earlier when digoxin and quinidine were administered together. Thus, a single dose of quinidine will increase the peak digoxin level when administered together with oral digoxin.
Cystic Fibrosis in a Black Woman
Authors: Clifford W. Lober
Journal: JAMA (1976)

CYSTIC FIBROSIS is a genetic disease (autosomal recessive) considered to have a striking racial distribution. Kulczycki and Schauf<sup>1</sup>estimated that this disease affects one of every 17,033 black newborns and is therefore 10 to 15 times less prevalent among black Americans than among white Americans. To our knowledge, there is only one report in the literature of cystic fibrosis in a black person over 20 years old.<sup>2</sup> <h3>Report of a Case</h3> A 22-year-old unmarried black secretary was seen by one of us (H.F.S.) in November 1972. She complained of a persistent, dull, abdominal pain. Since early childhood, she had had recurrent, aching abdominal discomfort and foul-smelling, floating stools. Two or three episodes of rectal prolapse had been noted each year since age 10. Many of her frequent "chest colds" (approximately ten each year) were accompanied by trace hemoptysis (&lt; 5 ml), but she had never experienced massive hemoptysis.
A Safe Technique for the Supraclavicular Brachial Plexus Block
Authors: Gale E. Dryden
Journal: JAMA (1963)

<h3>To the Editor:</h3> —A safe and simple technique for the supraclavicular brachial plexus block is to locate the plexus by palpation. The head must be turned to stretch the nerves, and the shoulder must be depressed so the clavicle will not cover the brachial plexus as it crosses the first rib. The palpating finger is placed in the angle formed by the clavicle and external jugular vein. The first rib, subclavian artery, and the insertions of the anterior scalenus and clavicular head of the sternocleidomastoid muscles are identified. Firm pressure is exerted in the region of insertion of the anterior scalenus, and the finger is moved along the rib until the nerves are crossed; the nerves are identified by their denser structure, tenderness, and, sometimes, paresthesia to the arm. The plexus is then held impinged between the finger and the rib until the block needle is inserted directly into the