tbuckley/cabot-search huggingface dataset:
Abstract P3-14-15: Lapatinib Plus Capecitabine in Trastuzumab Pre-Treated HER2- Positive Metastatic Breast Cancer: The Canadian Lapatinib Expanded Access Program Experience
Authors: J Chang, S Chia, C Prady, K Haider, D Grenier, P Lopez, S. Ghedira
Journal: Cancer Research (2010)

Abstract BACKGROUND: The global lapatinib expanded access programme (LEAP) provided access to lapatinib (L) combined with capecitabine (C) for women with HER2- positive metastatic breast cancer (MBC) who were previously treated with an anthracycline (A), taxane (T) and trastuzumab (TRAS) in 45 countries. The eligibility criteria and the dose of given drugs resembled that used in the phase III clinical trial EGF 100151, with the exception that patients (pts)previously exposed to C and pts with an ECOG performance status of 2 could be included as well. L is a dual tyrosine kinase inhibitor of EGFR and HER2. L plus C is an effective treatment option in T-refractory HER2-positive MBC. 148 Canadian pts were enrolled. METHODS: LEAP enrolled patients with ErbB2-positive, locally advanced and MBC showing progressive disease following prior therapies with A, T, TRAS-containing regimens. Pts received L (1,250 mg/day) and C (2,000 mg/m2/day, days 1-14, every 21 days). We analyzed 148 Canadian LEAP pts recruited from seven centres for demographics, duration of therapy, L compliance, left ventricular function, progression-free survival (PFS), and overall survival (OS). RESULTS: Data cut off for these analyses was Jan 10, 2010. [Data were not available for all 148 pts. The median age was 52 y (range 29-80 y) for 147 pts (145 women, 2 men). Ninety-five pts (64.6%) had no prior C and 52 (35.4%) had prior C (n=147). Study medication was discontinued for 142 pts (96.6%): 110 (74.8%) for progressive disease; 17 (11.6%) for adverse events; 8 (5.4%) for patient preference; and 3 (2%) were transitioned to the commercial supply of L. The median duration of therapy was 18.95 wk, ranging 0.1 to 96 wk (n=137). L compliance data showed that 73.7% of pts received ≥80% of the L dose (n=122). Median baseline left ventricular function (LVF) was 60%, ranging 50% to 81% (n=142). The median LVF at study end was 61%, ranging 37% to 83% (n = = 96). There was an amendment in June 2008 to end the collection of disease progression and/or death dates. Median PFS and OS were 22.1 wk (95% CI: 18.9-26.7), and 48 wk (95% CI: 42.3-…), respectively (n=71). CONCLUSIONS: L combined with C is an effective option for women with refractory HER2-positive MBC. The results seen in the Canadian subset enrolled in LEAP were similar to the results of EGF 100151 and the Global LEAP in the efficacy and safety data. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-14-15.
NICE guidance on laparoscopic surgery for inguinal hernias: Guidelines are less clinical excellence than hindrance
Authors: R K Choudhary
Journal: BMJ (2003)

EDITOR—We have two comments on the paper by Bloor et al on the impact of NICE guidance on laparoscopic surgery for inguinal hernias.1



Laparoscopic inguinal hernia repairs as percentage of all repairs before and after NICE guidance (15 March,p 578)



Firstly, the authors say that guidance from the National Institute for Clinical Excellence (NICE) on laparoscopic hernia repair …
Rhabdomyosarcoma of the toe
Authors: F. El Karak, S. Tabchi, E. El Rassy
Journal: BMJ (2014)

PC-SPES, a proprietary mixture composed of eight different herbs, is used worldwide as an alternative treatment by prostate cancer patients. It has been suggested that the clinical and in vitro antitumor activity exhibited by PC-SPES may be due to estrogenic activity, which in turn may be mediated by the presence of undeclared prescription drug contaminants. Here, we evaluated the in vivo effects of two different commercial lots of PC-SPES in male and female rats. Our high-pressure liquid chromatography analysis coupled with gas chromatography/mass spectrometry analysis by an independent laboratory suggested that PC-SPES lot 5430125 was contaminated with diethylstilbestrol (DES), whereas lot 5431249 was not. Treatment of male rats with PC-SPES lot 5430125 or DES alone reduced the weight of androgen target organs and decreased circulating levels of sex steroids and luteinizing hormone, whereas lot 5431249 was without effect. In addition, lot 5430125 and DES, but not lot 5431249 increased uterine weight in female rats. These results suggest that the inhibitory effects on androgen targets are mediated through suppression of the hypothalamic-pituitary axis and this suppression is probably due to DES contamination. We assessed the effects of both lots of PC-SPES and DES on hepatic cytochrome P450 expression and activity. Both lots of PC-SPES and DES reduced CYP3A activity and protein levels. Because the response of CYP3A to PC-SPES was not dependent on whether it contained DES, a phytochemical component of PC-SPES is most likely responsible for this effect. Inhibition of CYP3A has important implications for potential herbal-drug interactions.
Reassessing the Current UICC/AJCC TNM Staging for Renal Cell Carcinoma
Authors: Holger Moch, Walter Artibani, Brett Delahunt, Vincenzo Ficarra, Ruth Knuechel, Francesco Montorsi, Jean-Jacques Patard, Christian G. Stief, Tullio Sulser, Peter J. Wild
Journal: European Urology (2009)
SURVIVAL OF A HOMOLOGOUS PARATHYROID IMPLANT IN AN IMMUNOSUPPRESSED PATIENT
Authors: CarlG. Groth, WilliamS. Hammond, Shunzaburo Iwatsuki, Mordecai Popovtzer, Sergio Cascardo, CharlesG. Halgrimson, ThomasE. Starzl
Journal: The Lancet (1973)
Social, Institutional, and Economic Barriers to the Exercise of Patients' Rights
Authors: N G Levinsky
Journal: New England Journal of Medicine (1996)

During the past 30 years, the autonomy of patients has displaced beneficence on the part of physicians as the chief tenet of medical ethics.1 Respect for patients' autonomy is now considered fundamental to the practice of medicine. It is best exemplified by the universally recognized doctrine of informed consent. Patients have the right to information about their own medical care, as well as the right to accept or reject any recommended treatment. The physician formulates alternatives for dealing with a medical problem and advises the patient about the risks and benefits of these alternatives. The choice among them is the . . .
TOWEL SLING METHOD OF LIFTING PATIENT
Authors: Douglas P. Murphy
Journal: JAMA (1926)

An easy method of lifting, not commonly employed, is shown in the accompanying illustration. It is more comfortable to lifters and patient alike than the method in which both arms of the lifters are passed under the patient's body. By this method two can frequently do the work of three. A towel is passed under the lower part of the body. The near end is grasped in the left hand of the person at the patient's head. The far end is held in the assistant's right hand. The other arms are passed under the patient's body. The lifting is most comfortable when the towel ends are grasped with the thumbs up, as shown in the illustration.
Analysis of Liver Disease, Nuclear HBcAg, Viral Replication, and Hepatitis B Virus DNA in Liver and Serum of HBcAg Vs. Anti-HBe Positive Carriers of Hepatitis B Virus
Authors: Stephanos J. Hadziyannis, Harvey M. Lieberman, Gerassimos G. Karvountzis, David A. Shafritz
Journal: Hepatology (1983)

Nine HBeAg + and 24 anti-HBe + subjects with chronic hepatitis B virus (HBV) infection were studied for HBV DNA in the serum by molecular hybridization, for HBeAg in the liver by immunofluorescence, and for histologic evidence of liver disease. All HBeAg + patients had underlying chronic liver disease (chronic persistent hepatitis, chronic active hepatitis, or cirrhosis with or without hepatocellular carcinoma), and all were found positive for both HBV DNA in the serum and HBeAg in the nucleus of hepatocytes. Of the 24 anti-HBe + individuals, 18 had various forms of chronic liver disease. Six HBsAg + /anti-HBe + patients had normal liver histology except for numerous “ground-glass” hepatocytes with abundant cytoplasmic HBsAg. All six were negative for nuclear HBeAg and serum HBV DNA, but three showed HBV DNA which appeared to be integrated into unique sites in host liver DNA by hybridization analysis. In contrast, 14/18 (78%) of HBsAg + /anti-HBe + patients with chronic liver disease were positive for nuclear HBeAg, serum HBV DNA, or both of these markers of HBV replication. It is suggested that in long-term HBsAg carriers with serum anti-HBe and normal liver histology, viral replication is suppressed or inactive and HBV potential infectivity is presumably very low or absent. However, when viral replication is present in HBsAg + /anti-HBe + carriers (as demonstrated by serum HBV DNA and/or nuclear HBeAg), active liver disease is often found. In these individuals, active chronic liver disease appears to be related to continued replication and secretion of HBV and may occur in a much higher proportion of HBsAg + /anti-HBe + carriers than was previously suspected.
Former spy's death causes public health alert
Authors: Michael Day
Journal: BMJ (2006)

The death of the former Russian spy Alexander Litvinenko, linked to radiation poisoning, has caused a public health alert in London. 

After the discovery of highly dangerous radioactive polonium-210 in the dead man's body, the Health Protection Agency (HPA) called on anyone who visited the same places as Mr Litvinenko on 1 November to contact NHS Direct. 

The HPA said that more than 450 people had called the helpline and that details of 18 people had been passed on to them. 

As the BMJ went to press it emerged that three of the 18 were having tests at an …
Achieving successful ileal intubation during retrograde double balloon enteroscopy: description of a novel, alternative technique (with video)
Authors: E. Despott, C. Fraser
Journal: Endoscopy (2009)

In double-balloon enteroscopy (DBE), the retrograde approach is considered technically more challenging, with published failure rates for ileal intubation as high as 30 % [1]. The technique for ileal intubation described by Yamamoto et al. involves visualizing the ileocecal valve (ICV) while the overtube balloon is inflated in the ascending colon, followed by pull-back of the balloon to reduce the ileocolic angle (thus exposing the ICV) and then intubation of the ileum with the enteroscope, all in the forward view [2]. In our experience, and as evidenced by other published series, ileal intubation can still fail despite this maneuver [1] [3].
Why evidence is bad for your health
Authors: D. Spence
Journal: BMJ (2010)

Recently I spoke at a conference on implementing evidence based medicine. In particular, I asked why the robustly evidenced NHS quality and outcomes framework (QOF) has had no effect on outcomes. Is there something wrong with evidence based medicine? I opened the presentation to the floor to list the hidden weakness of “evidence.”

Commissioning bias — “No research, no evidence” is the most basic flaw of all. Drug companies are the only organisations with the resources and incentives to conduct research, so therapeutics dominate all evidence based medicine. And the industry investigates a …
Usefulness of Mammography in the Diagnosis and Management of Breast Disease in Postmenopausal Women
Authors: Ana M. Lamas
Journal: JAMA (1984)

We evaluated the clinical usefulness of mammography in postmenopausal women by conducting a "vertical" analysis using indexes of sensitivity and specificity, and a separate "horizontal" analysis assessing the relationship between the mammographic test result and the occurrence of specific clinical management decisions. The patients included 105 women with breast cancer, 104 women with fibrocystic breast disease, and 103 women with clinically benign breasts. Our study confirmed the generally accepted high values reported for the sensitivity and for the specificity of mammography as a test for breast cancer, while also helping to reconcile the widely varying indexes of test efficacy reported in some studies. We also observed that physicians' management decisions vary according to the mammographic interpretation, and include such distinctive clinical strategies as watchful expectancy (observe and follow), repeated mammograms, or breast biopsy. Future studies will need to determine reasons for specific management decisions, especially when they appear to contradict authoritative recommendations. (<i>JAMA</i>1984;252:2999-3002)
The electrocardiogram in acute dehydroemetine intoxication
Authors: L. A. SALAKO, A. O. DUROTOYE
Journal: Cardiovascular Research (1972)

Alterations in the electrocardiogram after intravenous administration of dehydroemetine were studied in rats. Disturbances of intraventricular conduction and slowing of the heart rate were the earliest changes observed. Prolongation of atrioventricular conduction time and complete heart block occurred at total doses greater than 10 mg/kg. Atrial extrasystoles and paroxysmal atrial tachycardia appeared in 16% of the animals after total doses of 15 mg/kg. Ventricular extrasystoles and paroxysmal ventricular tachycardia were never observed. The cause of death was always complete heart block with ventricular asystole. The action of dehydroemetine is cumulative, since repetition of the same dose, after normal electrocardiogram had been restored, resulted in more pronounced effects.
Changing Seasonality of Mortality From Coronary Heart Disease
Authors: Dimitrios Seretakis
Journal: JAMA (1997)

<h3>Context.</h3> —Coronary heart disease is the major cause of mortality in the United States. Factors associated with coronary risk are important to identify. Coronary mortality is greater during the winter months. <h3>Objective.</h3> —To investigate whether declining coronary mortality has been accompanied by a change in the seasonal pattern and to investigate the hypothesis that diminishing exposures to environmental cold and heat have affected the seasonal pattern. <h3>Design.</h3> —We used published data on coronary mortality by year to evaluate the time trend in the seasonal pattern. We fit a sine curve to the monthly frequency of deaths in each year and examined the trend over time in the ratio of the peak to the trough of the curve. <h3>Setting.</h3> —We used monthly coronary deaths in the United States from 1937 through 1991. Deaths by cause and month were not available by geographic area within the United States, but we were able to examine total monthly deaths in 2 regions with contrasting climates, New England and the South. <h3>Outcome Measures.</h3> —We used the yearly peak-to-trough ratio as our primary outcome and assessed its trend over time by linear regression. We also depicted the time trends using polynomial smoothing. <h3>Results.</h3> —The peak-to-trough ratio diminished by about 2% per year until around 1970, when the trend reversed. In New England, the decline was steeper than in the South, as measured from all deaths. <h3>Conclusion.</h3> —Seasonal patterns in coronary mortality in the United States have changed with time. These changes are compatible with the gradual expansion of adequate heating and the subsequent increased use of air-conditioning. Microclimatic influences on coronary mortality could explain in part the socioeconomic gradient of cardiovascular mortality.
AMPKα Modulation in Cancer Progression: Multilayer Integrative Analysis of the Whole Transcriptome in Asian Gastric Cancer
Authors: Yon Hui Kim, Han Liang, Xiuping Liu, Ju-Seog Lee, Jae Yong Cho, Jae-Ho Cheong, Hoguen Kim, Min Li, Thomas J. Downey, Matthew D. Dyer, Yongming Sun, Jingtao Sun, Ellen M. Beasley, Hyun Cheol Chung, Sung Hoon Noh, John N. Weinstein, Chang-Gong Liu, Garth Powis
Journal: Cancer Research (2012)

Abstract Gastric cancer is the most common cancer in Asia and most developing countries. Despite the use of multimodality therapeutics, it remains the second leading cause of cancer death in the world. To identify the molecular underpinnings of gastric cancer in the Asian population, we applied an RNA-sequencing approach to gastric tumor and noncancerous specimens, generating 680 million informative short reads to quantitatively characterize the entire transcriptome of gastric cancer (including mRNAs and miRNAs). A multilayer analysis was then developed to identify multiple types of transcriptional aberrations associated with different stages of gastric cancer, including differentially expressed mRNAs, recurrent somatic mutations, and key differentially expressed miRNAs. Through this approach, we identified the central metabolic regulator AMP-activated protein kinase (AMPK)α as a potential functional target in Asian gastric cancer. Furthermore, we experimentally showed the translational relevance of this gene as a potential therapeutic target for early-stage gastric cancer in Asian patients. Together, our findings not only provide a valuable information resource for identifying and elucidating the molecular mechanisms of Asian gastric cancer, but also represent a general integrative framework to develop more effective therapeutic targets. Cancer Res; 72(10); 2512–21. ©2012 AACR.
A Dose-dependent Effect of the Novel Inhaled Corticosteroid Ciclesonide on Airway Responsiveness to Adenosine-5 ′ -Monophosphate in Asthmatic Patients
Authors: DAVID A. TAYLOR, MARIANNE W. JENSEN, VARSHA KANABAR, RENATE ENGELSTÄTTER, VOLKER W. STEINIJANS, PETER J. BARNES, BRIAN J. O'CONNOR
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Inhaled corticosteroids decrease airway responsiveness in asthma partly through suppression of airway inflammation. We have previously demonstrated that inhaled budesonide reduced airway responsiveness to the mast cell stimulus adenosine-5 ′ -monophosphate (AMP) to a threefold greater extent than to methacholine and sodium metabisulfite, suggesting that AMP responsiveness may be a more sensitive marker of airway inflammation and steroid action in order to assess a dose–response relationship. To investigate this, we studied the effects of three doses of the novel corticosteroid ciclesonide (50 μ g, 200 μ g, and 800 μ g) inhaled as a dry powder twice daily on airway responsiveness to AMP and inflammatory parameters in induced sputum. In a three-parallel-dose group, double-blind, placebo-controlled, randomized, crossover study, with a washout period of 3 to 8 wk, a total of 29 patients with mild to moderate allergic asthma underwent AMP challenge and sputum induction before and after 14 d of treatment with ciclesonide or matched placebo. Compared with placebo, ciclesonide 100 μ g, 400 μ g, and 1,600 μ g daily reduced airway responsiveness to AMP by 1.6 (95% confidence interval [CI], − 0.1 to 3.4, not significant [NS]), 2.0 (95% CI, 0.4 to 3.6, p < 0.05), and 3.4 (95% CI, 2.3 to 4.4, p < 0.05) doubling doses, respectively, and this reduction in airway responsiveness was dose-dependent (p = 0.039). A significant reduction in the percentage of eosinophils in induced sputum was observed after 400 μ g and 1,600 μ g daily ciclesonide (p < 0.05), but this was not dose-dependent. Sputum eosinophil cationic protein (ECP) was significantly reduced after 400 μ g daily ciclesonide only (p < 0.05). Thus, in patients with mild to moderate asthma, assessment of airway responsiveness to AMP, rather than inflammatory parameters in induced sputum, represents a sensitive method to evaluate a dose–response relationship of an inhaled corticosteroid and may have applications in evaluating other novel inhaled corticosteroids.
Pulmonary Tularemia in Massachusetts
Authors: William E. R. Greer
Journal: New England Journal of Medicine (1948)

TULAREMIA is a relatively rare disease in New England. The pulmonary form, which is even less common, occurs in Massachusetts, as in the case reported below. It is important to recognize the presence of Pasteurella tularensis and its many reservoirs and transmitting agents, for a specific treatment is now available in streptomycin. Otherwise, the pulmonary form is fatal in 40 to 50 per cent of cases. Because of this fact a case of the pulmonary form occurring in a resident of Cape Cod who showed excellent response to streptomycin therapy is reported below.Tularemia has been reported in every New . . .
Ezh2 augments leukemogenicity by reinforcing differentiation blockage in acute myeloid leukemia
Authors: Satomi Tanaka, Satoru Miyagi, Goro Sashida, Tetsuhiro Chiba, Jin Yuan, Makiko Mochizuki-Kashio, Yutaka Suzuki, Sumio Sugano, Chiaki Nakaseko, Koutaro Yokote, Haruhiko Koseki, Atsushi Iwama
Journal: Blood (2012)
Fibrin and fibrinogen-related antigens in systemic sclerosis (scleroderma)
Authors: Vincent Falanga, Jonathan B. Kruskal, John J. Franks
Journal: Journal of the American Academy of Dermatology (1991)

Abnormalities in fibrin deposition are implicated in the pathogenesis of vascular occlusion in systemic sclerosis. We have used a technique that involves electrophoresis and densitometric analysis of captured fibrin- and fibrinogen-related antigens to measure the concentration of the individual fibrin and fibrinogen degradation products in 13 patients with systemic sclerosis and in 15 healthy control subjects. As a group, patients with systemic sclerosis had markedly elevated levels of total fibrin-related antigen (p = 0.0007) and D-dimer (p = 0.0004), the terminal degradation product of cross-linked fibrin. The levels of fibrin monomer, an intermediate product in the conversion of fibrinogen to cross-linked fibrin, and of D-monomer, a terminal breakdown fragment of fibrinogen and fibrin monomer, were also elevated (p less than 0.005). We conclude that patients with systemic sclerosis have evidence of enhanced fibrin formation and degradation.
Are swelling and aching of the legs reduced by operation on varicose veins?
Authors: M J Speakman, J Collin
Journal: BMJ (1986)

9 hommes et 17 femmes presentant des varices sont operes et les effets de la chirurgie sur les douleurs et sur le gonflement de la jambe sont etudies. Les resultats sont favorables. Les gonflements et douleurs devraient etre consideres comme des indications pour la chirurgie dans les cas de varices sans autres complications
Was It Leprosy?
Authors: D. C. Newman
Journal: JAMA (1895)

Spokane, Washington, Nov. 22, 1895.  To the Editor:  —My experience with lepers would point to Dr. McDougal's cases as being undoubtedly leprosy.  In the Sandwich Islands many cases can be found to disprove Dr. Ashmead's statement that if they were lepers the mother would have been infected too,  Dr. Geo. L. Fitch, of San Francisco, who was for some years medical officer at Honolulu and by whose courtesy I saw some hundreds of cases of leprosy, asserted that all the leprosy in the Islands among the natives was syphilis run riot in a virgin race, and defended his position so vigorously that the Government sent to Germany for Dr. Arnold to decide who was right. This was necessary as all lepers are sent to Molakai to the leper settlement from which place only death can relieve them.  Dr. Arnold's decision was in keeping with the opinion of all the old-time
Joint study of extracranial arterial occlusion. 8. Clinical-radiographic correlation of carotid bifurcation lesions in 177 patients with transient cerebral ischemic attacks
Authors: J. B. Gomensoro
Journal: JAMA (1973)

One hundred seventy-seven patients with transient ischemic attacks and a radiographic diagnosis of stenosis or occlusion at the cervical carotid artery bifurcation were included in our study. They were categorized by symptoms and type and extent of plaque. There were more smooth lesions reported in patients with less than 50% stenosis and more rough plaques in those with greater narrowing. Involvement of the cervical bifurcation by atherosclerosis presented a variable radiologic pattern. Seventy patients had unilateral stenosis; 83, bilateral stenosis; and 24, occlusion with contralateral stenosis. Smooth atheromata were described in 59 patients, rough in 87, and mixed lesions in 31. There was good correlation of the interpretation by the surgeon and the neuroradiologist when lesions were far-advanced or were roughened, and poor correlation when the lesions were minimal or smooth.