tbuckley/cabot-search huggingface dataset:
Tailored temozolomide therapy according to MGMT methylation status for elderly patients with acute myeloid leukemia
Authors: Bruno C. Medeiros, Holbrook E. Kohrt, Jason Gotlib, Steven E. Coutre, Bingyang Zhang, Daniel A. Arber, James L. Zehnder
Journal: American Journal of Hematology (2011)

Abstract Temozolomide sensitivity is determined by methylation of the O 6 ‐methylguanine‐DNA methyltransferase ( MGMT ) promoter. This study assessed whether the temozolomide dose can be tailored by MGMT promoter status and whether protracted, low‐dose temozolomide can “prime” blasts in patients with unmethylated MGMT (unMGMT). Elderly patients with high‐risk AML were stratified by MGMT methylation. Patients with methylated MGMT (mMGMT) received temozolomide 200 mg/m 2 orally for 7 days every 4 weeks, while patients with unMGMT received temozolomide 100 mg/m 2 orally for 14 days followed by 200 mg/m 2 orally for 7 days every 6weeks. Of 36 patients (median age, 75 years), 31 (86%) had an unMGMT promoter. Overall response rate for the entire cohort was 36%. Patients with mMGMT and unMGMT had similar response rates (40% vs. 29%). Median duration of response and overall survival (OS) among responders were 29 and 35 weeks, respectively. Induction deaths (ID) occurred in 25% of patients, mostly caused by disease progression. Hematological toxicities were the most common adverse event. Toxicities were similar between patients on conventional versus protracted schedules. High HCT‐CI scores were predictive of lower CR rate, higher ID, and shorter OS, while bone marrow blast count &lt;50% at screening predicted for improved responses. Temozolomide, dosed according to MGMT methylation status, demonstrated modest clinical activity in elderly patients with AML, especially in those presenting with fewer comorbidities and low disease burden. The trial was registered on www.ClinicalTrials.gov as #NCT00611247. Am. J. Hematol., 2012. © 2011 Wiley Periodicals, Inc.
Fats, Oil, Health
Authors: Vigen K. Babayan
Journal: JAMA (1990)

To the Editor.—  The American Medical Association's Council on Scientific Affairs 1 recently addressed the timely topic of saturated fatty acids in vegetable oils. Meats, dairy products, and hydrogenated vegetable oils provide over 90% of the fat consumed by the American public. While animal sources are mentioned in the article's abstract, hydrogenated vegetable oils are conspicuously absent. We fail to see why the Council on Scientific Affairs makes an issue of tropical oils, which represent a minor (3.5%) amount of the fat in the diet of the public. As the Council knows, the soybean oil producers were the first to raise this issue.  The article details the large amounts of the various fats and oils used by Americans. Of the 13 764 million pounds of vegetable oils consumed in this country annually, over 90% are hydrogenated vegetable oils (Table 3). Indeed, the hydrogenation is needed to provide the functional characteristics
A Case of Abscess of the Temporosphenoidal Lobe, Opened and Drained through the Osseous Auditory Meatus
Authors: A. Bronner
Journal: BMJ (1897)

JOURNAL of December 7th, I895, I recorded a case of cut throat, and the treatment of the case was summarised thus: October 5th, I894.Ligature of the common carotid artery in two places, of the internal jugular vein in two places, of the external and anterior jugular veins * perfusion of 20 ounces saline fluid.October 27th.SeconAary huemorrhage; attempted ligature of common carotid, which was rotten, so that tie ex-ternal and internal carotid arteries were tied, along with other ligatures on the internal jugular vein and a branch, by my colleague Mr. R. A. Bickersteth, who was fortunately at hand when the hoemorrhage occurred.November 5th.Hremorrhage from internal carotid artery arrested by packing and pressure.A quart of warm water in the rectum revived the patient.He was discharged on January 25th, 1895.After following his occupation-house painter-for nearly two years, he was admitted into the infirmary, under Dr. Caton, on December igth, 1896, on account of severe cough and pain in the right chest.He was very ill, with a high temperature and copious expectoration.He rapidly failed, and died on January 17th, 1897, two years and a-quarter after the injury, and two years after discharge from hospital.a. Small vessel dividing into lingual and superior thyroid.b.Left sympathetic nerve.c.Left pneumogastric nerve.d.Left common carotid artery ending in cicatrix.e. Left phrenic nerve.f.Leit internal jugular vein.q Right internal jugular vein.h.Right pneumogastric nerve.iRight common carotid artery.
The Use of Ethanol Injection under Endoscopic Control to Palliate Dysphagia Caused by Esophagogastric Cancer
Authors: L. S. Moreira, R. C. L. Coelho, R. U. Sadala, R. Dani
Journal: Endoscopy (1994)

Nine patients with dysphagia caused by unresectable tumors of the esophagus and cardia (eight with squamous-cell carcinomas and one with adenocarcinoma) were treated with absolute (95 g/l) alcohol mixed with 0.5% methylene blue. Total volumes ranging from 16 to 41 ml were injected endoscopically during sessions separated at 5-day intervals. The results were evaluated by endoscopic and radiological follow-up, as well as clinically, according to Bown's dysphagia score. Treatment had to be stopped in one patient with a preexisting esophagobronchial fistula. In the remaining eight patients, the mean dysphagia score decreased from 3.4 before treatment to 1.2 after treatment. After treatment, all patients were able to swallow a solid or semisolid diet. Treatment was repeated when dysphagia recurred, with a mean interval of 31.5 days between treatments. No complications were encountered. In our view, the preliminary results using this simple and inexpensive technique warrant comparative trials with other methods of palliation.
Abstract 2044: Down-regulation of YAP sensitizes lung cancer cells to platinum and ionizing radiation.
Authors: Haiying Cheng, Zhenfeng Zhang, Ruth Rodriguez-Barrueco, Jiyang Yu, Jose M. Silva, Simon Cheng, Roman Perez-Soler, Balazs Halmos
Journal: Cancer Research (2013)

Abstract Platinum compounds are the foundation of chemotherapy regimens for non-small cell lung cancer despite poor response rates and limited response duration. In order to identify novel target genes the modulation of which could influence drug sensitivity of lung cancer cells in response to cisplatin, we performed a high-throughput RNAi screen targeting the majority of genes in the human genome. We first transfected PC9 lung cancer cells with an shRNA library containing ∼60,000 individual shRNAs, then identified depleted versus enriched shRNAs following two weeks of cisplatin treatment versus vehicle in surviving cells. Standard quality control studies suggested good correlation among triplicates. After using strict selection criteria, we selected a narrow list of highly depleted genes- genes the activity of which is expected to be required for cell survival in the face of cisplatin therapy, including YAP (Yes associated protein). YAP shRNAs were depleted 80 fold in the cisplatin screen. YAP was initially identified as a protein interacting with the non-receptor tyrosine kinase c-Yes and is considered a nuclear effector of the Hippo pathway that promotes cell growth as a transcription co-activator. To validate this promising target identified in our screen, we first confirmed that an siRNA pool targeting YAP can efficiently knockdown YAP protein expression in multiple lung cancer cell lines, then next examined the effects of YAP knockdown on drug responses. YAP knockdown indeed quite prominently improved sensitivities not only to cisplatin, but also to ionizing radiation in several cell lines. Furthermore, YAP knockdown also induces prominent apoptosis as measured by induction of PARP cleavage concurrent with platinum therapy. Our findings indicate the YAP inhibition is potentially relevant to improve sensitivities to platinum-based chemotherapy and chemoradiation in lung cancer. Citation Format: Haiying Cheng, Zhenfeng Zhang, Ruth Rodriguez-Barrueco, Jiyang Yu, Jose M. Silva, Simon Cheng, Roman Perez-Soler, Balazs Halmos. Down-regulation of YAP sensitizes lung cancer cells to platinum and ionizing radiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2044. doi:10.1158/1538-7445.AM2013-2044
Population strategies to prevent smoking
Authors: Konrad Jamrozik
Journal: BMJ (2004)

Interventions targeted at individual smokers are only part of the much broader spectrum of strategies to reduce the prevalence of smoking. This article summarises the population strategies that can make substantial contributions to smoking cessation and help to prevent people from taking up smoking. Ten important initiatives are used or have been proposed for reducing tobacco use at population level. Nine initiatives are discussed here; the tenth (the use of proved treatments) is covered in previous articles in this series.

View this table:

Ten point plan for tobacco control



Policies that ban smoking in public places are effective in reducing passive smoking among non-smokers generally. They also protect vulnerable groups such as children and infants, adults with cardiac or respiratory disease, and pregnant women against the adverse effects of environmental tobacco smoke. Smoke-free policies in public places also send a clear message to young people about non-smoking being the norm, and they reduce the numbers of adults that young people see smoking.

In the workplace, smoke-free policies lead to some staff quitting—typically about 4% of the workforce—and reduce daily consumption among continuing smokers. Each extension of a smoke-free policy to a setting in which smoking was previously permitted requires both careful consideration of public opinion and systematic planning for the change. It is good practice to offer existing smokers in an organisation help in quitting during the lead-up to the introduction of a smoke-free policy, but most of those who quit in response to the change do so without special help.



Support for smoke-free restaurants in South Australia (smoke-free policy introduced in January 1999). Adapted from Miller et al (Aust N Z J Public Health 2002;26: 38-44



Support for smoke-free policies typically increases among smokers and non-smokers alike once the policies are introduced, and in the state of South Australia, for example, the …
Plans for cross border care costs to be met by home country are halted
Authors: Rory Watson
Journal: BMJ (2008)

Plans to clarify European Union rules for patients to receive reimbursable health care in countries other than their own have unexpectedly been put on hold after several EU commissioners strongly criticised them. The plans were due to have been presented on 19 December.

At least half a dozen of the 27 commissioners have lodged forceful objections to the proposal, which had been drafted by Markos Kyprianou, the health commissioner, and his advisers.

Some of the objections are openly political, given the sensitivity of healthcare issues and the fact that health care is the …
No benefit from using pulmonary artery catheters to guide treatment of acute lung injury
Authors: J T C Yen
Journal: Thorax (2006)

▴ National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med2006;354:2213–24 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Acute lung injury (ALI) is a prevalent and devastating condition in the intensive care unit. Although pulmonary artery catheters (PAC) provide clinicians with important data about a patient’s haemodynamic status, doubts about their clinical benefit and worries about safety have raised questions about their usefulness. This study was … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.volume%253D354%26rft.issue%253D21%26rft.spage%253D2213%26rft.epage%253D2224%26rft.atitle%253DPulmonary-artery%2Bversus%2Bcentral%2Bvenous%2Bcatheter%2Bto%2Bguide%2Btreatment%2Bof%2Bacute%2Blung%2Binjury.%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa061895%26rft_id%253Dinfo%253Apmid%252F16714768%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa061895&link_type=DOI [3]: /lookup/external-ref?access_num=16714768&link_type=MED&atom=%2Fthoraxjnl%2F61%2F9%2F804.atom [4]: /lookup/external-ref?access_num=000237758900003&link_type=ISI
Cancer risk of air pollution: epidemiological evidence.
Authors: K Hemminki, G Pershagen
Journal: Environmental Health Perspectives (1994)

Epidemiological studies on the effect of urban air pollution on lung cancer were surveyed. Overall, the studies from many countries point to a smoking-adjusted risk in urban areas over countryside areas that is higher by a factor of up to 1.5. The extent to which urban air pollution contributes to this excess remains unknown. Studies on diesel-exposed occupational groups show that urban air pollution may have a causative role in lung cancer. Model calculations on unit risk factors of known human carcinogens were carried out to rank carcinogens according to their current ambient air concentrations.
Mechanical ventilation at home
Authors: J W H Watt, K R Krishnan
Journal: BMJ (1989)

Mechanical ventilation at homeSIR,-We support Dr M A Branthwaite's succinct case for a nationally coordinated home ventilation service in Britain' Such a system would help smaller centres such as our own, which historically lacks the designated funding.At present we experience much difficulty in obtaining financial agreement for ventilators and associated equipment from patients' home districts, which prolongs their stay in hospital.The current impetus arises from the greater understanding of the treatability of nocturnal hypoxaemia associated with sleep apnoea or chronic pulmonary disease; numerically, these groups account for a large fraction of the total
Cyanosis with hepatic cirrhosis: A case with pulmonary arteriovenous shunting
Authors: A. J. Karlish, R. Marshall, L. Reid, S. Sherlock
Journal: Thorax (1967)

A case is reported of cirrhosis of the liver associated with cyanosis and finger clubbing in a man of 31 years. The chest radiograph showed diffuse nodular shadows in both lower zones. Pulmonary function tests gave an arterial oxygen saturation of 91% at rest, falling to 68% on exercise; the single breath diffusing capacity for carbon monoxide was reduced to 55% of the predicted value and there was an estimated right-to-left shunt of 23%. Post-mortem injection of the lungs with Micropaque-gelatin suspension showed numerous pleural spider naevi, denser over the lower lobes, arteriovenous communications in the infrahilar regions, including leashes of dilated vessels in pleural adhesions on the diaphragm and diffuse arterial vasodilatation in the lungs; although the injection mass could be traced into the pulmonary veins in only a few regions of the lung, the dilated arterioles and spiders were possible additional channels through which blood might be shunted from the alveolar surfaces. The very low arterial oxygen saturation on exercise was probably caused by a shunt greater than the 23% estimated at rest, but the low diffusing capacity may have been partly responsible. The cause of the low diffusing capacity remains uncertain.
Tick bite: two cases studied by scanning electron microscopy
Authors: K. AOKI, H. KAMATA, T. IIDA, H. SUZUKI
Journal: British Journal of Dermatology (1984)

The attachment of ticks to human skin has been studied by scanning electron microscopy. Intact specimens of Ixodes ovatus and Ixodes persulcatus were examined, and we also studied the skin of two patients who had been bitten by these two species. In the first case, the remains of the tick were visible and a homogeneous cement-like substance was observed on the dorsal hypostome and in the dermis, suggesting that the tick attaches itself to the host skin by a secretion. In the second case, the apices of some denticles of the hypostome were chipped. Two months later, the skin which the tick had attacked was biopsied and yellowish-brown particles, probably derived from the denticles, were seen in foreign body giant cells in the dermis.
Acute Obstructive Bronchiolitis
Authors: Charles Harris
Journal: JAMA (1965)

DURING THE PAST 25 years, acute obstructive bronchiolitis, by being cast into the broad category of bronchopneumonia, has all but vanished from the medical literature and tables of vital statistics. Yet, 100 years ago it was a well-described entity, known then as capillary bronchitis.<sup>1-3</sup>Impressed by its asphyxial nature, Morgagni and Laennec called it catarrh suffocante.<sup>1</sup>The cases recently reported by Ham<sup>4</sup>reemphasize both its critical nature and the fact that it can attack young adults with no history of lung disease. In its pure form, it can readily be confused with pulmonary edema, asthma, and bronchopneumonia. <h3>Report of a Case</h3> A 72-year-old woman was admitted for low-grade fever and malaise. Harsh breath sounds were heard over the lung fields. She was given tetracycline and the temperature returned to normal the next day, although some moist rales were heard posteriorly. On the fourth day, however, fever (102
Schering-Plough is accused of overcharging and of obstructing justice
Authors: F. Charatan
Journal: BMJ (2003)

Last month Schering-Plough, based in Kenilworth, New Jersey, said that it faced indictment on a number of charges listed in a letter from the US Attorney's Office in Boston for the District of Massachusetts.

The charges included giving financial grants and other items of value to doctors and other customers, marketing drugs for unapproved uses—so-called off-label uses—and submitting false drug prices to the government so that Medicaid paid too much for …
Fibreoptic bronchoscopy today: a review of 255 cases.
Authors: J B Macdonald
Journal: BMJ (1975)

An analysis of 255 fibreoptic bronchoscopies showed that the major indication for bronchoscopy was suspected bronchial carcinoma (93% of cases). Of the 183 patients finally shown to have bronchial carcinoma 83% had abnormal bronchoscopy findings and 65% had bronchial biopsy specimens diagnostic of malignancy. These figures were superior to those obtainable with rigid bronchoscopy, particularly with upper lobe and peripheral tumours. Brush biopsy and bronchography were useful supplementary techniques. Sputum cytology gave poorer results than fibreoptic bronchoscopy, but enabled diagnosis in some otherwise undiagnosed cases. The complication rate was low and the claim of this new technique to be the investigation of choice in bronchial carcinoma seemed to be justified in clinical practice.
Care of the Postoperative Surgical Patient
Authors: William G. Abel
Journal: JAMA (1986)

This work from the United Kingdom is a pleasant surprise. It correctly emphasizes that postsurgical care is a multidisciplinary responsibility and that no one surgeon can expect to be an expert in all the areas of postoperative management, although exceptions may exist. The interrelationships of antimicrobials, pharmacologic agents, analgesics, and nutritional support are discussed in some detail, along with the added perturbing influences of anesthesia and surgery. A minor disadvantage is the review of some drugs not available in this country. The book is divided into five parts and 15 chapters, which makes retrieval of information relatively easy. Chapter 1 covers the period from leaving the operating room up until leaving the recovery room. The first part presents general information, including mortality statistics, and the remainder covers specific medical problems and their causes and treatment. Chapter 2, "Case for Patient Controlled Analgesia," highlights an important point, viz, too many patients
A piece of my mind. Educational malpractice
Authors: S. Stitham
Journal: JAMA (1991)

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Maternal Pregnancy Levels of Polychlorinated Biphenyls and Risk of Hypospadias and Cryptorchidism in Male Offspring
Authors: Katherine A. McGlynn, Xuguang Guo, Barry I. Graubard, John W. Brock, Mark A. Klebanoff, Matthew P. Longnecker
Journal: Environmental Health Perspectives (2009)

The etiologies of the male urogenital anomalies cryptorchidism and hypospadias are poorly understood. It has been suggested, however, that in utero hormone levels may be related to risk. Endocrine-disrupting chemicals, including polychlorinated biphenyl (PCB) compounds, may alter hormone levels and thereby affect the fetus.To examine whether in utero PCB exposure is related to cryptorchidism and hypospadias, we examined PCB levels among pregnant women enrolled in the Collaborative Perinatal Project (CPP).The CPP enrolled pregnant women at 12 U.S. medical centers between 1959 and 1965. For the present research, we analyzed third-trimester serum samples from the mothers of 230 sons with cryptorchidism, 201 sons with hypospadias, and 593 sons with neither condition. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression and examined the associations of each anomaly with individual PCB congener levels, sum of PCBs, and several functional groupings of PCBs.In general, the ORs for cryptorchidism or hypospadias showed no notable associations with individual PCB congener levels or functional groupings of PCBs. However, the ORs and 95% CIs for the sum of PCBs associated with hypospadias were as follows: 0-1.9 microg/L, reference group; 2-2.9 microg/L, OR = 1.57, 95% CI, 1.05-2.34; 3-3.9 microg/L, OR = 1.45, 95% CI, 0.90-2.34; and > or = 4.0 microg/L, OR = 1.69, 95% CI, 1.06-2.68; p-value for trend = 0.08.Given the large number of associations examined, these findings do not strongly support the hypothesis that PCBs are associated with cryptorchidism or hypospadias. Because population serum PCB levels at the time of sample collection were considerably higher than levels at present, it is unlikely that current PCB exposure is related to the development of either anomaly.