tbuckley/cabot-search huggingface dataset:
Indications for Endoscopic Nd-YAG Laser Surgery in the Trachea and Bronchus
Authors: K. Oho, I. Ogawa, R. Amemiya, T. Ohtani, R. Yamada, O. Taira, Y. Hayata
Journal: Endoscopy (1983)

Nd-YAG laser surgery via the fiberoptic bronchoscope can vaporize lesions causing airway obstruction or stenosis located from the trachea to segmental bronchi with minimized danger of bleeding, and improve ventilatory disturbances. 35 lesions in the trachea and bronchus consisting of 27 malignant lesions and 8 benign lesions were treated with endoscopic Nd-YAG laser surgery. The procedures were performed under local anesthesia, and no significant side effects were recognized. The lesions was irradiated with 20-80 W. power. In most cases a continuous wave was used, but in cases of early stage squamous cell carcinoma intermittent irradiation of 0.5 second laser spots were used. In 21 of 35 cases effective results were obtained. The non-effective results obtained in 14 cases were considered to be due to inexact preprocedural evaluation of the extent of the lesions. Effective results were obtained in 11 of 13 lesions located in the trachea, in 3 of 5 lesions in the trachea and bronchus and in 7 of 17 lesions in the bronchus. Tumor in the trachea with severe ventilatory disturbance is a good indication for Nd-YAG laser surgery to rapidly alleviate symptoms. But in cases of lung cancer, indications even as a palliative procedure are limited to those cases in which the lung parenchyma distal to the stenotic portion is viable. However, the indications for this procedure as a curative modality are extremely limited.
P368Guanabenz interferes with ER stress and exerts protective effects in cardiac myocytes
Authors: C Neuber, J Uebeler, T Schulze, H Sotoud, A El-Armouche, T Eschenhagen
Journal: Cardiovascular Research (2014)

Background: Endoplasmic reticulum (ER) stress has been implicated in a variety of cardiovascular diseases. In the setting of ER stress, disruption of the complex of protein phosphatase 1 regulatory subunit 15A and catalytic subunit of protein phosphatase 1 (PPP1R15A-PP1c) by the small molecule guanabenz (antihypertensive, a2-adrenoceptor agonist) and subsequent inhibition of stress-induced dephosphorylation of eukaryotic translation initiation factor 2α (eIF2α) results in prolonged eIF2a phosphorylation, inhibition of protein synthesis and protection from ER stress. In this study we assessed if guanabenz protects against ER stress in cardiac myocytes and affects the functional behaviour of 3 dimensional engineered heart tissue (EHT). Methods and Results: We utilized 2D neonatal rat cardiac myocytes for the assessment of cell viability and activation of ER stress-signalling pathways and 3D engineered heart tissue (EHT) for functional analysis. The main findings were: (i) Tunicamycin induced ER stress as measured by increased mRNA and protein levels of glucose-regulated protein 78 kDa (GRP78), P-eIF2α, activating transcription factor 4 (ATF4), C/EBP homology protein (CHOP), and cell death. (ii) Guanabenz had no measurable effect when applied alone, but antagonized the effects of tunicamycin on ER stress markers. (iii) Tunicamycin and other known inducers of ER stress (hydrogen peroxide, doxorubicin, thapsigargin) induced cardiac myocyte death and this was antagonized by guanabenz in a concentration- and time-dependent manner. (iv) ER stressors also induced acute or delayed contractile dysfunction in spontaneously beating EHTs and this was, with the notable exception of relaxation deficits under thapsigargin, not significantly affected by guanabenz. Conclusion: The data confirm that guanabenz interferes with ER stress-signalling and has protective effects on cell survival. Data show for the first time that this concept also applies to cardiac myocytes. The modest protection in EHTs point to more complex mechanisms of force regulation in intact functional heart muscle.
Minocycline-Induced Pigmentation at Sites of Cutaneous Inflammation
Authors: Neil A. Fenske
Journal: JAMA (1980)

In four cases of minocycline hydrochloride-induced cutaneous pigmentation, blue-gray discoloration in sites of cutaneous inflammation was seen in all cases. An additional finding of generalized, brown hyperpigmentation with accentuation in sun-exposed areas was noted in one. Although all of the patients had used relatively high doses of medication, the variable duration of therapy before pigmentary changes and dearth of similar reports suggest an idiosyncratic response to this commonly used medication. Histochemical stains and electron microscopic studies suggest hemosiderin or a pigment with similar staining properties; a minocycline degradation product, however, cannot be discounted.
Combined Use of Clofibrate and Cholestyramine or DEAE Sephadex in Hypercholesterolaemia
Authors: A. N. Howard, D. E. Hyams
Journal: BMJ (1971)

A comparison was made of the effect of DEAE (diethylaminoethyl) Sephadex (an anion exchange resin) and cholestyramine (Questran) with and without the addition of clofibrate in normal and hypercholesterolaemic patients. DEAE Sephadex (12-15 g/day) alone appeared to be as effective as cholestyramine in lowering the plasma cholesterol by 12-15%. Clofibrate acted synergistically with DEAE Sephadex and increased the activity of the latter by over twofold. This combination proved superior to that of clofibrate and cholestyramine and has the greatest potential use in the treatment of type II pattern hyperlipoproteinaemia.
The Cambridge World History of Human Disease
Authors: William K. Beatty
Journal: JAMA (1994)

Every individual and institution interested in and involved with the history of human diseases will find this an important reference work. Kiple and the Cambridge University Press set out to portray the history of human diseases from many angles and in substantial detail, to provide a starting place for researchers, and to "encapsulate" what this generation knows about the field. They have achieved their goals.
691. Efficient Downregulation of ENaC Activity by Synthetic siRNAs
Authors: Christa M. Schmidt, Stephanie Huth, Olga Mykhaylyk, Christian Plank, Carsten Rudolph, Joseph Rosenecker
Journal: Molecular Therapy (2006)

The amiloride-sensitive epithelial sodium channel (ENaC) is assumed to play a major role in the pathogenesis of chronic lung disease in cystic fibrosis patients. Its natural regulation by the cystic fibrosis transmembrane conductance regulator (CFTR) appears to be compromised, based on the impaired function of CFTR. The missing inhibition of the channel results in increased absorption of sodium ions and fluid across airway epithelia leading to the depletion of the airway surface liquid (ASL) layer and to the depression of mucociliar clearance. Several observations suggest that a downregulation of ENaC restores the periciliar liquid layer, thereby rehydrating the mucus and improving ciliary clearance in the lung. Therefore, we attempt to specifically downregulate ENaC expression by RNA interference. ENaC is a tetrameric ion channel localized in the apical membrane of epithelia. It is comprised of three subunits alpha, beta and gamma. Alpha ENaC itself is the pore forming subunit. To study the downregulation of the subunits by RNAi we designed ENaC-specific synthetic and plasmid based siRNA sequences. To analyze RNAi for ENaC expression we used the murine renal cortical collecting duct cell line M-1. This cell line is well characterized for ENaC expression; in addition we detected a strong amiloride dependent signal in a fluorescence based assay capable of measuring changes in the cells membrane potential. To identify optimal siRNA transfection conditions for M-1 cells we used a GFP expressing M-1 cell line. The highest GFP knockdown was achieved when using HiPerFect (Qiagen) in combination with CombiMag (OZ Biosciences). After 72h a GFP knockdown to 40% was detected by fluorescence measurements. To identify alpha ENaC knockdown we analyzed six different siRNA sequences designed by conventional design programs. In addition we included a sequence tested by Li and Folkesson against rat ENaC adapted to the murine sequence. These sequences were transfected in M-1 epithelial cells in 6-well format; the knockdown is analyzed on mRNA and protein level via quantitative real-time PCR and Western blotting. The most efficient ENaC knockdown resulting in 70% reduction was achieved with the modified sequence published by Li and Folkesson 2005. These results suggest that ENaC activity can be inhibited with synthetic siRNAs which might lead to a functional effect on the sodium transport.
Diagnostic Features of a Unilateral Fused Kidney with a Lower-Pole Inflamed, Hemorrhagic Cyst
Authors: RICHARD T. TRACKLER, DAVID O. KATZMAN, HAROLD G. COONS
Journal: Clinical Nuclear Medicine (1979)

Numerous imaging procedures contributed to the diagnosis of unilateral fused kidney with an associated lower-pole mass in a 68-year-old man with back and right lower quadrant pain. 99mTc-DMSA renal scintigraphy provided the best global picture of the renal anomaly and of a lower-pole contour defect suggesting a mass.
Pilotropic mycosis fungoides presenting with multiple cysts, comedones and alopecia
Authors: None FRASER-ANDREWS, None ASHTON, None RUSSELL-JONES
Journal: British Journal of Dermatology (1999)

We report a 45‐year‐old man with mycosis fungoides (MF) who presented with multiple epidermoid cysts, comedones and alopecia and who responded to treatment with intravenous and oral cyclophosphamide. The pilotropic variant of MF, characterized histologically by follicular lesions and pilotropism without mucinosis, is uncommon and often resistant to treatment.
The Privacy of the Doctor's Office
Authors: G. G. Liddle
Journal: JAMA (1966)

To the Editor:—  Doctors get large quantities of free mail. Some complain about this, but I love it. I can sit back in my chair and sort the postman's gifts. I am important, as I toss 1 1/4 cent mailings into the wastebasket with a sneer. Look at the stupid picture on this one. What is he selling? A fountain pen that writes from right to left. Does it work? Maybe the office nurse would like the free sample. Thus runs the gullibility of the medical profession. I have been steered as the advertiser intended, and my advertising mail is not really meant for me at all.  The truth of this was emphasized by a recent arrival, offering a large loan of $3,000 to $50,000 without cosigners through a cooperative bank. The obscure grammar in this offer is unimportant. The sentence following told me that I might obtain, by returning
GANGRENE OF FINGER DUE TO SCLERODERMA
Authors: Julius Gottesman
Journal: JAMA (1924)

There are few references in the literature relative to gangrene complicating scleroderma. Although trophic disturbances and superficial necroses, especially over prominent and bony points, are quite common in this condition, actual gangrene involving large amounts of tissue is rarely mentioned. Cohen1recently described two cases that came under his observation, both involving the fingers. Mracek2and Buerger3mention the possibility of this complication.  The mechanism of the process is obvious. As the thickening and infiltration of the skin progress, there is increasing pressure on the blood vessels, gradually obliterating them and closing off the circulation.  REPORT OF CASE  D. E., a woman, aged 28, admitted to Montefiore Hospital, Sept. 1, 1922, complained of pain and stiffness of the joints, especially the small joints of the hands. The family history and past history was irrelevant. The present illness began about two and one half years before, when the
Morbidity from chronic asthma.
Authors: J L Stellman, J E Spicer, R M Cayton
Journal: Thorax (1982)

Seventy asthmatic patients newly referred to a hospital outpatient clinic have been studied. In one-third of the patients the diagnosis of asthma had not been considered. Eight patients presented with an FEV1 of one litre or less. Acute severe asthma is commonly believed to precede death from asthma, but patients with more chronic symptoms may have equally severe airways obstruction without appearing acutely ill. Failure to diagnose and treat such patients may be contributing to our present inability to reduce the death rate from asthma.
Methylation of Polycomb Target Genes in Intestinal Cancer Is Mediated by Inflammation
Authors: Maria A. Hahn, Torsten Hahn, Dong-Hyun Lee, R. Steven Esworthy, Byung-wook Kim, Arthur D. Riggs, Fong-Fong Chu, Gerd P. Pfeifer
Journal: Cancer Research (2008)

Abstract Epigenetic changes are strongly associated with cancer development. DNA hypermethylation is associated with gene silencing and is often observed in CpG islands. Recently, it was suggested that aberrant CpG island methylation in tumors is directed by Polycomb (PcG) proteins. However, specific mechanisms responsible for methylation of PcG target genes in cancer are not known. Chronic infection and inflammation contribute to up to 25% of all cancers worldwide. Using glutathione peroxidase, Gpx1 and Gpx2, double knockout (Gpx1/2-KO) mice as a model of inflammatory bowel disease predisposing to intestinal cancer, we analyzed genome-wide DNA methylation in the mouse ileum during chronic inflammation, aging, and cancer. We found that inflammation leads to aberrant DNA methylation in PcG target genes, with 70% of the ∼250 genes methylated in the inflamed tissue being PcG targets in embryonic stem cells and 59% of the methylated genes being marked by H3K27 trimethylation in the ileum of adult wild-type mice. Acquisition of DNA methylation at CpG islands in the ileum of Gpx1/2-KO mice frequently correlates with loss of H3K27 trimethylation at the same loci. Inflammation-associated DNA methylation occurs preferentially in tissue-specific silent genes and, importantly, is much more frequently represented in tumors than is age-dependent DNA methylation. Sixty percent of aberrant methylation found in tumors is also present in the inflamed tissue. In summary, inflammation creates a signature of aberrant DNA methylation, which is observed later in the malignant tissue and is directed by the PcG complex. [Cancer Res 2008;68(24):10280–9]
Innate Immune Response Profiles and Their Relationship to the Frequency of Respiratory Illnesses in the First Three Years of Life
Authors: C. Virnig, T. Pappas, K. Roberg, E. Anderson, D. DaSilva, L. Salazar, C. Tisler, M. Evans, R. Gangnon, J. Gern
Journal: Journal of Allergy and Clinical Immunology (2009)
Health Effects of Climate Change
Authors: Andy Haines
Journal: JAMA (2004)

HUMANS ARE NOW MAKING UNprecedented changes to the global environment. Economic development has been fostered by the use of fossil fuels but the accompanying accumulation of greenhouse gases, particularly carbon dioxide and methane, has implications for the world’s climate (BOX). Since the 1850s when temperature records began, the world has warmed by approximately 0.6°C, largely in the last 3 decades. The United Nations Intergovernmental Panel on Climate Change (IPCC) projects an increase of between 1.8°C and 5.8°C and an increase in sea levels between 9 and 88 cm during the next century. Warming is likely to be greater at the poles than at the equator. The residence time in the atmosphere of carbon dioxide exceeds 100 years; therefore, our actions affect the prospects of future generations. The IPCC concluded, “There is now good evidence that regional changes in climate, particularly increases in temperature, have already affected a diverse set of physical and biological systems in many parts of the world.” Earlier break-up of ice on rivers and lakes and movements of plant and animal ranges to higher altitudes are some examples. There is also potential for large-scale and potentially irreversible changes in Earth systems, such as slowing of the ocean circulation that transports warm water to the North Atlantic, large-scale melting of the Greenland and west Antarctic ice sheets, and accelerated global warming because of the positive feedbacks of the carbon cycle (eg, methane released from thawing arctic tundra). The probability of these events may be very low but is likely to be affected by the speed and duration of climate change. The potential pathways by which climate change may affect health are shown in the FIGURE.
Mary Winifred Hart (nee Sawday)
Authors: A. Green
Journal: BMJ (2010)

Interspecialty referrals for increasingly complex hospital inpatients are common and miscommunication often leads to delays in patient care. In a district general hospital, a web-based system generated an email referral, which lacked visibility and tracking/audit of the process, with no record generated automatically in paper inpatient notes or electronic patient records (EPR). We aimed to improve the visibility and safety of the interspecialty referral system. We canvassed stakeholders, informally and via an online satisfaction survey, collecting qualitative and quantitative data about attitudes to the existing system, generating ideas for change. We process mapped the system, identifying points of weakness. We adapted our EPR system, using a work-around solution, to develop a form that could be emailed from the EPR. This generated a permanent record within the EPR and an electronic record of the referral having been sent. We measured the visibility of referrals and responses within the EPR. We generated an online training ‘how-to’ video and reaudited stakeholder satisfaction. There was a significant increase in the proportion of junior doctors satisfied or very satisfied with the interspecialty referral system (27/31 postintervention; 87.1% vs 26/55 preintervention; 47%; p&lt;0.0001) and more believed that the visibility was adequate or very adequate (24/31 postintervention; 77.4% vs 9/55 preintervention; 16.4%; p&lt;0.0001). Visibility of referrals by project team members on the EPR increased from a baseline of 3.5% to 83.6% and the visibility of responses to these referrals on the EPR increased from 4.6% to 40.7%. Qualitative feedback was excellent, hospital executive approval was gained and our work-around system spread to non-team members. We developed a more visible and reliable interspecialty referral system, adapting existing EPR capabilities, which was popular with users and led to cultural change in interspecialty referral responders. A formal EPR redesign, informed by our project, is in development.
Tribunal suspends GP after he told patient who was threatening suicide to go ahead
Authors: C. Dyer
Journal: BMJ (2014)

A GP who told a patient to “jolly well go and do it now” after she threatened to kill herself has been suspended for three months by a fitness to practise panel.

Arun Singhal, 65, also told the patient, “If you don’t know how to do it, it’s on the internet.” He was unaware that she was secretly recording the consultation.

A panel of the Medical Practitioners Tribunal Service concluded that Singhal had probably not taken seriously the suicide threats of the woman, referred …
Shorter radiotherapy course just as effective for treating breast cancer, research finds
Authors: J. Wise
Journal: BMJ (2013)

Fewer, higher doses of radiotherapy given over a shorter treatment time are as safe and effective at treating early breast cancer as a longer course, the 10 year results of two large studies have confirmed.

The results of the UK Standardisation of Breast Radiotherapy (START) trials confirm the earlier five year findings and support current practice in the United Kingdom. A short course of 15 treatments given over three weeks …
Languages as evolving organisms –<i>The</i>solution to the logical problem of language evolution?
Authors: Christina Behme
Journal: Behavioral and Brain Sciences (2008)

Abstract Christiansen &amp; Chater (C&amp;C) argue persuasively that Universal Grammar (UG) could not have arisen through evolutionary processes. I provide additional suggestions to strengthen the argument against UG evolution. Further, I suggest that C&amp;C's solution to the logical problem of language evolution faces several problems. Widening the focus to mechanisms of general cognition and inclusion of animal communication research might overcome these problems.
Wakefield is struck off for the "serious and wide-ranging findings against him"
Authors: Z. Kmietowicz
Journal: BMJ (2010)

Andrew Wakefield, the British gastroenterologist who sparked a worldwide scare over the measles, mumps, and rubella (MMR) vaccine, has been found guilty of serious professional misconduct and struck off the medical register by the General Medical Council.

In its summation of the case against Dr Wakefield the GMC fitness to practise panel concluded that erasing Dr Wakefield’s name from the medical register was “the only sanction that is appropriate to protect patients and is in the wider public interest, including the maintenance of public trust and confidence in the profession and is proportionate to the serious and wide-ranging findings made against him.”

Dr Wakefield now has 28 days to appeal against the judgment before he is officially struck off.

In January Dr Wakefield was found guilty of dishonesty and irresponsibility by the GMC, the UK’s regulatory body. The fitness to practise panel held that Dr …
Robust T-cell stimulation by Epstein-Barr virus–transformed B cells after antigen targeting to DEC-205
Authors: Carol S. Leung, Michael A. Maurer, Sonja Meixlsperger, Anne Lippmann, Cheolho Cheong, Jianmin Zuo, Tracey A. Haigh, Graham S. Taylor, Christian Münz
Journal: Blood (2013)
Activated NF-kB in Colorectal Cancer: Predictive or Prognostic Factor?
Authors: Giovanni Brandi, Maria A. Pantaleo, Guido Biasco, Paola Paterini
Journal: Journal of Clinical Oncology (2008)

of nutrients declines with age, it is reasonable to hypothesize that the bioavailability of oral drugs is reduced in the elderly.Likewise, phase II studies may be the best opportunity to assess the influence of liver function which declines with age on the area under the curve of drugs undergoing hepatic metabolism. 3urria emphasizes that approximately 60% of all cancers occur in patients age 65 and older, whereas the average age of patients involved in clinical trials is at least 10 years younger than that.Thus, in reality, an older patient treated with a United States Food and Drug Administration (FDA)-approved agent could be considered a trial given that information obtained from younger patients may not be applicable to older patients.We would strongly encourage the FDA to consider mandating phase II trials of new agents for older people, in view of the abundant evidence that age is associated with significant pharmacologic changes, and that data obtained in young adults should not be applied automatically to the older ones.A government intervention appears necessary.We would also like to challenge the pharmaceutical industry to start on its own studies of older individuals.Given the high proportion of older cancer patients receiving therapy, it is equally important to demonstrate the effectiveness and safety of antineoplastic drugs in younger and older populations.We sincerely hope that the study of Hochster et al will inspire the FDA to take action long overdue.This has become even more urgent with the current evidence that age may be a risk factor for late complications of cancer treatment such as acute myeloid leukemia 4 and chronic cardiomyopathy. 5n conclusion, we would like to emphasize Hurria's suggestion that future studies in older individuals include the estimate of a patient's physiologic age, based on functional and biochemical parameters that have been widely described in the last few years. 6, the members of the Geriatric Oncology Consortium, are committed to conducting clinical trials in older individuals by assessing their physiologic age and their particular age-related needs.