tbuckley/cabot-search huggingface dataset:
An Address Delivered at the Opening of the Section of Obstetrics
Authors: W. J. Smyly
Journal: BMJ (1891)

in hlifn we have a careful observer and a conscientious worker, anid onie wlhose mnethods we will do well to imitate.Biefore I conielude 1 would wish it to be understood that there is another side to this picture, or perhaps it may be the same picture looked at from a different standpoint.It is that muchlharm may be done by too excessive attention to riest.Evil may resuilt from too prolonged rest.Mechanical rest may, in one sense, be antagonistic to physiological rest.Mechanical rest, in many caseXs, must be interfered with in order to attain physiological rest.An example will best showv my meaning.Immediately after an injury the effasions inlto the tissues may, by their presence, interfere withl the normal blood current through the part.At a later (late these effusions are replaced by organised ma- oerial whlich will also act in tl( same way.The nerve equi- libriunm will also be altered.The part will then be, from the vascular and nervous side, in a state of physiological unrest, and this unrest wvill be intensified by prolonged mechanical rest, because, unless there is a normal blood current, the effusions anid fibrous material will not be removed.It is therefore necessary that, whlile we maintain mechanical rest after a part is injjured, we should at the same time adopt somiie incains to remove these products.It is here that mass- a.ge' (Ais so vlaluable; lightly applied it has a marked soothing iiiniuenice oni the nerve disturbance; more strongly, though still gently applied, it will get rid of the effusions by causilng, a temiiporary congestion and free flow of blood throughl the part; still more strongly applied, it breaks down fibrous adhesions anid gets rid of the pain felt in certain movements of the limb.Whlile the massage interferes wvith f lie meiclhanical rest, it acts directly in relieving the physiol.)-icalunrest.Experience alone will tell how far we can go wvtih inassage in order to attain the one object-tlhe pliysio- loical rest--while at the samne time we avoid doing harm by its over-use by interfering with the mechanical rest.In aeute sprains and strainis it may be begun at once, gently nig,lht and moirning, using elastic pressure witlh wadding and a flainiiel bandage in the intervals of the massage.In sub-
PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial
Authors: Frederick J Raal, Evan A Stein, Robert Dufour, Traci Turner, Fernando Civeira, Lesley Burgess, Gisle Langslet, Russell Scott, Anders G Olsson, David Sullivan, G Kees Hovingh, Bertrand Cariou, Ioanna Gouni-Berthold, Ransi Somaratne, Ian Bridges, Rob Scott, Scott M Wasserman, Daniel Gaudet
Journal: The Lancet (2014)
Body Weight and Diabetes
Authors: Alfred A. Rimm
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The findings reported by O'Sullivan inThe Journal(1982; 248;949) that body weight in patients with normal gestational glucose tolerance test results is not related to diabetes have a serious flaw. With only 66 obese subjects in the normal control group, the author had only a 12% chance to detect a relationship between relative weight and diabetes. Therefore, it is not surprising that no relationship was found. This low chance of detection is based on the assumption that obese patients have a relative risk of 1.82 for diabetes. This assumption was obtained using the women who had previous transient gestational glucose intolerance. The incidence of diabetes in the obese women in this group (46.7%) was divided by the incidence of diabetes in the nonobese group (25.6%). Therefore, if obesity confers a risk of 1.82 for diabetes, there is a 88% chance that this risk level (or lower)
Value of the History and Physical in Identifying Patients at Increased Risk for Coronary Artery Disease
Authors: David B. Pryor
Journal: Annals of Internal Medicine (1993)

Objective: To determine whether information from the physician's initial evaluation of patients with suspected coronary artery disease predicts coronary anatomy at catheterization and 3-year survival. Design: Prospective validation of regression model estimates in an outpatient cohort. Setting: University medical center. Patients: A total of 1030 consecutive outpatients referred for noninvasive testing for suspected coronary artery disease; 168 of these patients subsequently underwent catheterization within 90 days. Measurements: Information from the initial history, physical examination, electrocardiogram, and chest radiograph was used to predict coronary anatomy (the likelihood of any significant coronary disease, severe disease [left main or three-vessel], and significant left main disease) among 168 catheterized patients and to estimate 3-year survival among all patients. These estimates were compared with those based on treadmill testing. Cardiovascular testing charges were calculated for all patients. Results: Predicted coronary anatomy and survival closely corresponded to actual findings. Compared with the treadmill exercise test, initial evaluation was slightly better able to distinguish patients with or without any coronary disease and was similar in the ability to identify patients at increased risk for dying or with anatomically severe disease. Based on arbitrary definitions, 37% to 66% of patients were at low risk and responsible for 31% to 56% of the charges for cardiovascular testing. Conclusions: The physician's initial evaluation, despite the subjective nature of much of the information gathered, can be used to identify patients likely to benefit from further testing. The development of strategies for cost-conscious quality care must begin with the history, physical examination, and simple laboratory testing.
Discrimination in medicine
Authors: R. MacDonald
Journal: BMJ (2002)

As the current political situation in France shows, discrimination is rife. So why should the situation in medicine be any different? The 50 rapid responses to our recent editorial on racism in medicine are proof that discrimination in medicine is alive and well.1 This is hardly surprising in a culture where a consultant surgeon thinks there is nothing wrong in saying to a junior: “You are not operating on bloody Nigerians here. You are operating on normal human beings.”2

But discrimination has many forms, not just racial. At a time where more than 60% of students applying to British medical schools are female, only 6% of consultant surgeons are women. 3 4 In addition, over 90% of women want to work part …
Peptic Ulcer: A profile
Authors: J. Fry
Journal: BMJ (1964)

After a short time in general practice I realized that the peptic ulcers I was encountering were quite different from those I had treated in hospital. I got the impression that peptic ulcers had a characteristic natural history with a marked tendency towards natural remissions which were really uninfluenced by my efforts at medical treatment. Reports by Malmros and Hiertonn (1949), Martin and Lewis (1949), Rae and Allison (1953), and Doll, Friedlander, and Pygott (1956) tended to support my views. I set out to record the course and natural history of peptic ulcer in my practice, and this paper presents the findings over the past 15 years (1948-63).
USSR and US Health Policies
Authors: John A. D. Cooper
Journal: New England Journal of Medicine (1972)

AN article in this issue of the Journal reports on the visit of a United States Health Delegation to the USSR in 1970. Another group, which traveled to the Soviet Union in 1970 on a similar mission,1 visited different institutions and programs over a somewhat longer period. From information obtained by the two groups, and from "The Soviet Five-Year Plan for Public Health, 1971–1975,"2 interesting comparisons can be drawn between the development of health care and the education of health professionals in the Soviet Union and the United States.In many ways, health policies in the two countries offer striking . . .
The Role of Erlotinib (Tarceva, OSI 774) in the Treatment of Non-Small Cell Lung Cancer
Authors: Roman Perez-Soler
Journal: Clinical Cancer Research (2004)

Abstract Erlotinib (Tarceva) is a reversible and highly specific inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. Phase I studies established a fixed daily oral dose of 150 mg as the recommended dose for Phase II studies. Using this dose and schedule, the response rate in a group of 57 patients with EGFR-positive non-small cell lung cancer after failure of platinum-containing chemotherapy was 12%. The median survival was 8.4 months, and the 1-year survival was 40%. Occurrence and severity of rash were correlated with an improved survival independently of performance status. Another ongoing Phase II study in 50 patients with bronchoalveolar carcinoma has shown a response rate of 26%. Results from two Phase III front-line studies in combination with chemotherapy, TALENT and TRIBUTE, have been recently reported. The addition of erlotinib did not improve response rate, time to progression, or survival. Efforts in the continued development of erlotinib should be focused on the following: (a) investigating the reasons for the lack of relationship between EGFR expression and clinical outcome; (b) the reasons for the failure of the front-line combination trials; and (c) confirming the rash/clinical outcome relationship. Progress in these tasks will allow a better selection of patients who can benefit from this therapy, permit the development of more effective combination schedules with cytotoxics, and define whether this agent should be used at the optimal biological dose or at the maximum-tolerated dose.
The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: efficacy, safety, and pharmacokinetics.
Authors: J Corne, R Djukanovic, L Thomas, J Warner, L Botta, B Grandordy, D Gygax, C Heusser, F Patalano, W Richardson, E Kilchherr, T Staehelin, F Davis, W Gordon, L Sun, R Liou, G Wang, T W Chang, S Holgate
Journal: Journal of Clinical Investigation (1997)

CGP 51901 is a non-anaphylactogenic mouse/human chimeric anti-human IgE antibody that binds to free IgE and surface IgE of IgE-expressing B cells but not to IgE bound to high affinity IgE receptors (Fc epsilonR1) on mast cells and basophils or low affinity IgE receptors (Fc epsilonR2) on other cells. A phase 1 double-blind, placebo-controlled, single dose study with doses of 3, 10, 30, and 100 mg of CGP 51901 was conducted in 33 pollen-sensitive subjects who had raised levels of serum IgE and received either intravenous CGP 51901 or placebo. The administration of CGP 51901 was well tolerated and resulted in a decrease of serum free IgE levels in a dose-dependent manner, with suppression after 100 mg of CGP 51901 reaching > 96%. Time of recovery to 50% of baseline IgE correlated with the dose of administered antibody and ranged from a mean of 1.3 d for the 3 mg to 39 d for the 100 mg dose. Total IgE, comprised of free and complexed IgE, increased as stored and newly synthesized IgE bound to CGP 51901. Complexed IgE was eliminated at a rate comparable with the terminal half-life of free CGP 51901 (11-13 d at all doses). Only one subject showed a weak antibody response against CGP 51901. We conclude that the use of anti-human IgE antibody is safe and effective in reducing serum IgE levels in atopic individuals and provides a potential therapeutic approach to the treatment of atopic diseases.
Revival of an Old Battle: Intermittent vs. Continuous Positive-Pressure Breathing
Authors: Claude Lenfant
Journal: New England Journal of Medicine (1970)

For nearly 30 years the relative advantages of continuous pressure breathing (CPB) and of intermittent pressure breathing (IPB) have been the object of a controversy. The proponents of CPB had their first hour of glory during World War II. The development of new aircraft capable of reaching higher altitudes led to the use of CPB to gain altitude tolerance for the pilot by an increase in the overall pressure in the lung and therefore in the partial pressure of oxygen. For this purpose, there was no doubt that CPB was better than IPB because it is difficult to obtain so . . .
Royal college calls for national priorities setting
Authors: J. Smith
Journal: BMJ (1995)

The Royal College of Physicians is calling for a national council to help determine priorities in the health service (see also p761). In launching the college's report, Setting Priorities in the NHS: A Framework for Decision Making, the president, Sir Leslie Turnberg, emphasised that choices had to be made within the NHS since not everything that was possible was affordable.

The report argues that equity for the whole population is more important than freedom of individual choice but says that the criteria for setting priorities must be open. Sir Leslie said that there was confusion about who was taking decisions on …
MID-WALL STRIAE PATTERN ON LATE GADOLINIUM ENHANCEMENT IMAGING PREDICTS FUTURE CARDIOVASCULAR EVENTS IN PATIENTS WITH SYSTOLIC DYSFUNCTION
Authors: Fahad Saleh Almehmadi, Immaculate Nevis, Mohammad Zahrani, Mahmoud Bokhari, John Stirrat, Raymond Yee, James A. White
Journal: Journal of the American College of Cardiology (2013)
Impact of Primary Prophylaxis With Granulocyte Colony-Stimulating Factor on Febrile Neutropenia and Mortality in Adult Cancer Patients Receiving Chemotherapy: A Systematic Review
Authors: Nicole M. Kuderer, David C. Dale, Jeffrey Crawford, Gary H. Lyman
Journal: Journal of Clinical Oncology (2007)

Randomized controlled trials (RCTs) of prophylactic granulocyte colony-stimulating factors (G-CSF) have demonstrated a significant reduction in febrile neutropenia (FN) after systemic chemotherapy. Several RCTs have been published recently that investigate the impact of G-CSF on mortality and relative dose-intensity (RDI).A comprehensive systematic review and meta-analysis of all reported RCTs comparing primary prophylactic G-CSF with placebo or untreated controls in adult solid tumor and malignant lymphoma patients was undertaken without language restrictions, using electronic databases, conference proceedings, and hand-searching techniques. Two reviewers extracted data independently. Summary estimates of relative risk (RR) with 95% CIs were estimated based on the method of Mantel-Haenszel and DerSimonian and Laird.Seventeen RCTs were identified including 3,493 patients. For infection-related mortality, RR reduction with G-CSF compared with controls was 45% (RR = 0.55; 95% CI, 0.33 to 0.90; P = .018); for early mortality (all-cause mortality during chemotherapy period), it was 40% (RR = 0.60; 95% CI, 0.43 to 0.83; P = .002); and for FN, it was 46% (RR = 0.54; 95% CI, 0.43 to 0.67; P < .001). Average RDI was significantly higher in patients who received G-CSF compared with control patients (P < .001). Bone or musculoskeletal pain was reported in 10.4% of controls and 19.6% of G-CSF patients (RR = 4.03; 95% CI, 2.15 to 7.52; P < .001). Significant reductions in FN with G-CSF were observed in studies allowing secondary G-CSF prophylaxis in controls and in the three trials with concurrent prophylactic antibiotics in both treatment arms.Prophylactic G-CSF reduces the risk of FN and early deaths, including infection-related mortality, while increasing RDI and musculoskeletal pain. There are insufficient data to assess the impact of G-CSF on disease-free and overall survival.
FoxO Transcription Factors Promote AKT Ser473 Phosphorylation and Renal Tumor Growth in Response to Pharmacologic Inhibition of the PI3K–AKT Pathway
Authors: Aifu Lin, Hai-long Piao, Li Zhuang, Dos D. Sarbassov, Li Ma, Boyi Gan
Journal: Cancer Research (2014)

The PI3K-AKT pathway is hyperactivated in many human cancers, and several drugs to inhibit this pathway, including the PI3K/mTOR dual inhibitor NVP-BEZ235, are currently being tested in various preclinical and clinical trials. It has been shown that pharmacologic inhibition of the PI3K-AKT pathway results in feedback activation of other oncogenic signaling pathways, which likely will limit the clinical utilization of these inhibitors in cancer treatment. However, the underlying mechanisms of such feedback regulation remain incompletely understood. The PI3K-AKT pathway is a validated therapeutic target in renal cell carcinoma (RCC). Here, we show that FoxO transcription factors serve to promote AKT phosphorylation at Ser473 in response to NVP-BEZ235 treatment in renal cancer cells. Inactivation of FoxO attenuated NVP-BEZ235-induced AKT Ser473 phosphorylation and rendered renal cancer cells more susceptible to NVP-BEZ235-mediated cell growth suppression in vitro and tumor shrinkage in vivo. Mechanistically, we showed that FoxOs upregulated the expression of Rictor, an essential component of MTOR complex 2, in response to NVP-BEZ235 treatment and revealed that Rictor is a key downstream target of FoxOs in NVP-BEZ235-mediated feedback regulation. Finally, we show that FoxOs similarly modulate the feedback response on AKT Ser473 phosphorylation and renal tumor growth by other phosphoinositide 3-kinase (PI3K) or AKT inhibitor treatment. Together, our study reveals a novel mechanism of PI3K-AKT inhibition-mediated feedback regulation and may identify FoxO as a novel biomarker to stratify patients with RCC for PI3K or AKT inhibitor treatment, or a novel therapeutic target to synergize with PI3K-AKT inhibition in RCC treatment.
Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis B virus
Authors: Masataka Tsuge, Nobuhiko Hiraga, Hideki Takaishi, Chiemi Noguchi, Hiromi Oga, Michio Imamura, Shoichi Takahashi, Eiji Iwao, Yoshifumi Fujimoto, Hidenori Ochi, Kazuaki Chayama, Chise Tateno, Katsutoshi Yoshizato
Journal: Hepatology (2005)

Abstract Studies of hepatitis B virus (HBV) mutants have been hampered by the lack of a small animal model with long-term infection of cloned HBV. Using a mouse model in which liver cells were highly replaced with human hepatocytes that survived over a long time with mature human hepatocyte function, we performed transmission experiments of HBV. Human serum containing HBV and the virus produced in HepG2 cell lines that transiently or stably transfected with 1.4 genome length HBV DNA were inoculated. Genetically modified e-antigen–negative mutant strain also was produced and inoculated into the mouse model. A high-level (≈1010 copies/mL) viremia was observed in mice inoculated with HBV-positive human serum samples. The level of viremia tended to be high in mice with a continuously high human hepatocyte replacement index. High levels and long-lasting viremia also were observed in mice injected with the in vitro generated HBV. The viremia continued up to 22 weeks until death or killing. Passage experiments showed that the serum of these mice contained infectious HBV. Genetically engineered hepatitis B e antigen–negative mutant clone also was shown to be infectious. Lamivudine effectively reduced the level of viremia in these infected mice. In conclusion , this mouse model of HBV infection is a useful tool for the study of HBV virology and evaluation of anti-HBV drugs. Our results indicate that HBeAg is dispensable for active viral production and transmission. (Hepatology 2005;42:1046–1054.)
Secretion of immunoreactive calcitonin by human breast carcinomas.
Authors: R C Coombes, G C Easty, S I Detre, C J Hillyard, U Stevens, S I Girgis, L S Galante, L Heywood, I Macintyre, A M Neville
Journal: BMJ (1975)

Twenty-three out of 28 patients with metastatic breast carcinoma and one out of 13 patients with localised disease had raised levels of plasma immunoreactive calcitonin. Monolayer cultures of breast carcinomas maintained for up to 10 weeks released immunoreactive calcitonin, and a primary breast carcinoma passaged in "nude" mice for over a year contained material immunologically and chromatographically resembling the monomeric form of human calcitonin. These studies indicate that breast carcinomas can produce calcitonin and that plasma calcitonin measurements may be useful in staging patients with breast carcinomas.
Sex‐related differences in the initiation of allergic rhinitis in mice
Authors: T. Yamatomo, M. Okano, T. Ono, E. Nakayama, T. Yoshino, A. R. Satoskar, D. A. Harn Jr, K. Nishizaki
Journal: Allergy (2001)

Background: Several clinical and epidemiologic studies have investigated sex differences in the prevalence of allergic rhinitis. At present, however, no reports have demonstrated such differences in experimental models with local, but not parenteral, sensitization with antigens that may reflect natural exposure to allergens. We have recently developed murine models of allergic rhinitis after repeated intranasal sensitization with antigens in the absence of adjuvants. In this study, we investigated the role of sex in the initiation of the disease in vivo . Methods: Male and female CBA/J and BALB/c mice were sensitized intranasally with phospholipase A 2 (PLA 2 ) and Schistosoma mansoni egg antigen (SEA), respectively, in the absence of adjuvants. After the repeated sensitization, serum Ab titers against the sensitizing antigen and nasal eosinophilia were determined. In addition, the involvement of androgen in IgE synthesis was investigated in castrated CBA/J male mice with or without testosterone administration. Results: Females produced significantly higher levels of PLA 2 ‐specific IgE than males in CBA/J mice sensitized with PLA 2 . On the other hand, both titers of PLA 2 ‐specific IgG1 and nasal eosinophilia did not significantly differ between the two groups. Castrated male mice produced significantly higher amounts of PLA 2 ‐specific IgE than sham‐treated male mice. In addition, PLA 2 ‐specific IgE production decreased in castrated mice treated with testosterone. Sexual differences in the production of Ag‐specific IgE were not seen in BALB/c mice after the sensitization with SEA. Conclusions: These results suggest that sex is responsible for the production of Ag‐specific IgE, but not IgG1 or nasal eosinophilia, and that androgen appears to be involved in the in vivo production of specific IgE in male mice.
Comparison of Partial Nephrectomy and Percutaneous Ablation for cT1 Renal Masses
Authors: R. Houston Thompson, Tom Atwell, Grant Schmit, Christine M. Lohse, A. Nicholas Kurup, Adam Weisbrod, Sarah P. Psutka, Suzanne B. Stewart, Matthew R. Callstrom, John C. Cheville, Stephen A. Boorjian, Bradley C. Leibovich
Journal: European Urology (2014)