tbuckley/cabot-search huggingface dataset:
PD05-06: Determination of HER2 Status with Analysis of Plasma DNA by Digital PCR in Patients with Metastatic Breast Cancer.
Authors: MK Graeser, H Gevensleben, IE Smith, A Ashworth, NC Turner
Journal: Cancer Research (2011)

Abstract Background. A small proportion of originally HER2 negative primary breast cancers relapse with HER2 amplified disease. Identification of these cancers is important as these patients may benefit from HER2 targeting therapies. A proportion of free plasma DNA originates from the cancer, and accurate determination of HER2 copy number in plasma DNA has the potential to non-invasively determine HER2 status in patients with metastatic breast cancer. Digital PCR can differentiate small increases in DNA concentration with a much higher degree of accuracy than conventional quantitative PCR, and here we assess the potential of plasma DNA digital PCR to determine HER2 status. Methods. We examined a cohort of 44 patients with metastatic breast cancer treated at the Royal Marsden Hospital who had received a median of 1.5 prior courses of chemotherapy for recurrent disease; 34 patients had ER positive and 9 HER2 positive (all 3+ positive HercepTest) disease as determined on biopsy of recurrent disease in 16 patients and original primary cancer in 28 patients. Following informed consent, plasma samples were taken, free plasma DNA was extracted and concentration determined with LINE1 quantitative PCR. We designed a custom HER2 copy number TaqMan MBG-probe (Applied Biosystems) and two chromosome 17 peri-centromeric control probes TUFMP1 and UBBP4, avoiding known SNPs and regions of normal copy number variation. Digital PCR was performed in 384 well format on a 7900HT Fast RT-PCR system, with copy number ratio determined using the Poisson distribution. Results. HER2 Digital PCR assay was initially tested on DNA from 9 HER2 amplified cell lines. HER2/UPPB4 ratio was increased in 9/9 HER2 amplified cell lines, and HER2/TUFMP1 in 7/9 due to co-amplification of the 17q peri-centromeric DNA in 2 cell lines. Dilution experiments with SKBR3 DNA in non-amplified DNA demonstrated sensitivity down to ∼1% levels. We selected HER2/UBBP4 digital PCR for examination of patient samples. Plasma DNA Digital PCR HER2/UBBP4 ratios differed substantially between HER2 non-amplified (mean 1.047, SD 0.149, median 1.046, range 0.70−1.264), and HER2 amplified cancers (median 2.231, range 1.138−7.89, p&amp;lt;0.001). Digital PCR HER2 ratios had a high diagnostic accuracy with ROC curve AUC 0.967 (95% CI 0.585−0.997). With a threshold Digital PCR HER2 ratio of 1.3 the test had 100% specificity and 89% sensitivity, with negative predictive value 97%. The single miscalled HER2 amplified patient had a low tumour burden. Results of a test set using sequential probability ratio test analysis will be presented at the conference. Conclusions: Plasma DNA Digital PCR accurately determined HER2 status in patients with metastatic breast cancer. Analyses of plasma DNA have the potential to replace biopsy sampling of metastatic disease to guided targeted therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD05-06.
A CASE OF WOODY PHLEGMON OF THE NECK (PHLEGMON LIGNEUX)
Authors: G. Parker
Journal: BMJ (1914)

uheldifficulty.He sways muclh on standing and feels giddy, but does not fall even with hiis eyes shult.There is no rigid-ity of any muscle.Tlhere is, no nystagmius; tle pupil reactions and ophthalmoscopic appearances are niormial.The fields of visioni are neatly normiial, but there is a certain amount of limitationa, equal in all directionis, oln the left side.There is slighlt ptosis oni eachl side.Speeclh is somewhat explo- s-ive aind at tle same time scanning.It was this defect in spechi more thlani aniythling else that miade himn give up his workl.rJ'l1ere is nlo affection of senlsation in any part.The knee-jerks are exaggerated.There is no ankle clonus.The plantar reflex is-flexor.There is no affec- tion of thie sphincters, but solmie frequeilcy of mictutritioln-- about twelve timies ini the twenity-four hours, inciluding once or twice at niglht, when lhe is comnpelled to get up for that ptIrpose.The qtuatity of urine in the twenity-four hours is only about 60 oz., anid it appears to be normnial.(C.B. P., the eldest brothier of tlhe family, was also
Benign Esophageal Polyp With Barrett's Syndrome
Authors: Micha Shapira
Journal: JAMA (1979)

ECTOPIC gastric mucosa in the esophagus was first reported about 70 years ago<sup>1</sup>by Keible. In 1950 Barrett<sup>2</sup>described a syndrome, now identified with his name, of a chronic peptic ulcer in the middle third of the esophagus lined with columnar epithelium distal to the ulcer. Since Barrett's initial description, several reports of columnar-lined esophagus have appeared. The relation of this condition to reflux esophagitis and a high incidence of adenocarcinoma has been reported.<sup>3</sup> We present a case report of a patient with hiatal hernia and reflux esophagitis in whom a columnar-lined epithelium developed (Barrett's syndrome) in a benign polyp of the lower esophagus. This benign polyp had been diagnosed 16 years previously. <h3>Report of a Case</h3> A 68-year-old woman was first seen by a physician in 1961. She complained of dysphagia, heartburn, and intermittent epigastric pain. Roentgenographic examination showed a polyp in the lower part of
SUBTROPICAL TRACHOMAWITH SPECIAL RELATION TO A NEW REMEDY IN ITS TREATMENT.
Authors: RUFFIN A. WRIGHT
Journal: JAMA (1903)

and in vigorous health.The attending surgeon placed the leg in plaster cast from the first, for six weeks.When the cast was removed it was found to be ununited; a new fixed dressing was applied and the patient put on crutches and treatment continued for six weeks, with the patient walking about, with the same unsuccessful result.He was again placed in bed with pulley extension for six weeks more when he was brought to the hospital for the purpose of cutting down and wiring the ends together.The ends were found separated by muscular tissue and fascia a full inch.The
The Population History of Extant and Extinct Hyenas
Authors: Nadin Rohland, Joshua L. Pollack, Doris Nagel, Cédric Beauval, Jean Airvaux, Svante Pääbo, Michael Hofreiter
Journal: Molecular Biology and Evolution (2005)

We have analyzed partial DNA sequences of the mitochondrial cytochrome b gene from extant striped, brown, and spotted hyenas as well as from Pleistocene cave hyenas. Sequences of the Pleistocene cave hyenas from Eurasia and modern spotted hyenas from Africa are intermixed in phylogenetic analyses, questioning any taxonomic delineation between the two groups. Contrary to cave hyenas in Eurasia, spotted hyenas in Africa show a phylogeographic pattern with little geographical overlap between two mitochondrial DNA (mtDNA) clades, suggesting two Pleistocene refugia in the north and south of Africa. Our results, furthermore, suggest three waves of migration from Africa to Eurasia for spotted hyenas, around 3, 1, and 0.3 MYA. A recent emigration of striped hyenas from Africa to Eurasia took place less than 0.1 MYA, resulting in a dramatic expansion of the geographical range of striped hyenas. In striped hyenas and within the geographical range of mtDNA clades in spotted hyenas, we found identical sequences several thousand kilometers apart, indicating a high rate of migration during the Pleistocene as well as the Holocene. Both striped and brown hyenas show low amounts of genetic diversity, with the latter ones displaying just a single haplotype.
The Time Is Now for Gene- and Genome-Based Bacterial Diagnostics
Authors: Garth D. Ehrlich, J. Christopher Post
Journal: JAMA Internal Medicine (2013)

Clinicalmicrobiology ispoised tomove into adynamic ageby embracing molecular diagnostic techniques, such as polymerase chain reaction–based amplification techniques and whole-genome sequencing (WGS). These technologies will revolutionize data acquisition for theranostics and the tracking of outbreaks. Whole-genome sequencing originally proved its worth through investigations of infectious agents.1 In this issue of JAMA Internal Medicine, Reuter et al2 now advocate WGS for routine diagnostics and public health microbiology. These ideas arenot as far-fetchedas they may initially sound. Although the cost and time to conductWGSwouldhaveoncebeenprohibitive,abacterialWGS can be performed for less than $100 in 1 day’s time.Moreover, the computational systems forperforming theanalytics on the WGSdata allow for rapid turnaround times.Collectively, these metrics make WGS competitive with any technology, including traditional methods of culturing bacteria. Although there arenocommercialWGSanalytics thatcould integratewithstandard laboratory informationsystemsnow,suchtoolswill bedeveloped that canaccess cloud-basedcomputing resources containingglobalstraindatabasesannotatedwithrespect toclinical origins, spread, and associated symptoms.
A Focal Source of Atrial Fibrillation Treated by Discrete Radiofrequency Ablation
Authors: Pierre Jai¨s, Michel Hai¨ssaguerre, Dipen C. Shah, Salah Chouairi, Laurent Gencel, Me´le`ze Hocini, Jacques Cle´menty
Journal: Circulation (1997)

Atrial fibrillation is usually thought to be due to multiple circulating reentrant wavelets. From previous studies, a focal mechanism is considered to be very unlikely. In this report, focal atrial fibrillation is defined on an ECG pattern of atrial fibrillation and later demonstrated to be due to a focal source.Nine patients (five men and four women, age, 38 +/- 7 years) with paroxysmal focal atrial fibrillation are reported here. All were free of structural heart disease and had frequent episodes of atrial fibrillation despite the use of a mean of 4 +/- 2 antiarrhythmic drugs. Atrial fibrillation was associated with runs of irregular atrial tachycardia or monomorphic extrasystoles. The electrophysiological study demonstrated that all the atrial arrhythmias were due to the same focus firing irregularly and exhibiting a consistent and centrifugal pattern of activation. Three foci were found to be located in the right atrium, two near the sinus node and one in the ostium of the coronary sinus. Six others were located in the left atrium at the ostium of the right pulmonary veins (n = 5) and at the ostium of the left superior pulmonary vein (n = 1). All atrial arrhythmias were successfully treated by use of a mean of 4 +/- 4 radiofrequency pulses.In some patients, the surface ECG pattern of atrial fibrillation is due to a focal rapidly firing source of activity that can be eliminated by discrete radiofrequency energy applications.
A Case-Control Study of Baldness in Relation to Myocardial Infarction in Men
Authors: Samuel M Lesko
Journal: JAMA (1993)

<h3>Objective.</h3> —To examine the relationship between male pattern baldness and the risk of myocardial infarction in men under the age of 55 years. <h3>Design and Participants.</h3> —A hospital-based, case-control study was conducted in eastern Massachusetts and Rhode Island. Cases were men admitted to a hospital for a first nonfatal myocardial infarction (n=665); controls were men admitted to the same hospitals with noncardiac diagnoses (n=772). Extent of baldness was assessed using the 12-point modified Hamilton Baldness Scale; other information was obtained by personal interview. Among the controls, the prevalence of any baldness was 34%, while the prevalence of baldness involving the vertex scalp was 23%. <h3>Results.</h3> —After allowing for age, the relative risk estimate for frontal baldness compared with no hair loss was 0.9 (95% confidence interval, 0.6 to 1.3), for baldness involving the vertex scalp it was 1.4 (95% confidence interval, 1.2 to 1.9). Risk of myocardial infarction increased as the degree of vertex baldness increased (<i>P</i>&lt;.01); for severe vertex baldness the relative risk was 3.4 (95% confidence interval, 1.7 to 7.0). The relationship between vertex baldness and myocardial infarction was consistent within strata defined by age and other risk factors for coronary artery disease. <h3>Conclusion.</h3> —These data support the hypothesis that male pattern baldness involving the vertex scalp is associated with coronary artery disease in men under the age of 55 years. (<i>JAMA</i>. 1993;269:998-1003)
Pneumothorax in AIDS
Authors: Kent A. Sepkowitz, Edward E. Telzak, Jonathan W. M. Gold, Edward M. Bernard, Steve Blum, Melanie Carrow, Mark Dickmeyer, Donald Armstrong
Journal: Annals of Internal Medicine (1991)

Objective: To determine risk factors for the development of pneumothorax in patients with the acquired immunodeficiency syndrome (AIDS). Design: Prospective cohort study. Setting: Tertiary care center. Patients: Of 1030 patients with AIDS who were followed at Memorial Sloan-Kettering Cancer Center between 1 January 1980 and 30 September 1989, 20 (2%) developed pneumothorax that was unrelated to trauma or a pulmonary procedure. Results: Of 20 patients with AIDS who presented with pneumothorax, 19 had compelling evidence of concurrent Pneumocystis carinii pneumonia. Using bivariate analysis, patients receiving aerosol pentamidine prophylaxis (relative risk, 17.6) and those with a history of P. carinii pneumonia (relative risk, 14.5) were more likely to develop pneumothorax. By Mantel-Haenszel stratified analysis, aerosol pentamidine use was a statistically significant risk factor independent of a history of P. carinii pneumonia. The pneumothorax-related mortality rate was 10% and there was considerable morbidity. Conclusions: Patients with AIDS at the highest risk for developing pneumothorax are those with a history of P. carinii pneumonia who are receiving aerosol pentamidine prophylaxis but who nevertheless develop P. carinii pneumonia. The benefits of aerosol pentamidine prophylaxis in these patients far outweigh this risk. Pneumocystis carinii pneumonia should be considered as the most likely diagnosis in any patient with AIDS who develops a pneumothorax.
Oxidative Stress Activates SIRT2 to Deacetylate and Stimulate Phosphoglycerate Mutase
Authors: Yanping Xu, Fulong Li, Lei Lv, Tingting Li, Xin Zhou, Chu-Xia Deng, Kun-Liang Guan, Qun-Ying Lei, Yue Xiong
Journal: Cancer Research (2014)

Glycolytic enzyme phosphoglycerate mutase (PGAM) plays an important role in coordinating energy production with generation of reducing power and the biosynthesis of nucleotide precursors and amino acids. Inhibition of PGAM by small RNAi or small molecule attenuates cell proliferation and tumor growth. PGAM activity is commonly upregulated in tumor cells, but how PGAM activity is regulated in vivo remains poorly understood. Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2. Increased levels of reactive oxygen species stimulate PGAM2 deacetylation and activity by promoting its interaction with SIRT2. Substitution of endogenous PGAM2 with an acetylation mimetic mutant K100Q reduces cellular NADPH production and inhibits cell proliferation and tumor growth. These results reveal a mechanism of PGAM2 regulation and NADPH homeostasis in response to oxidative stress that impacts cell proliferation and tumor growth.
Otto Gerhard Prokop
Authors: N. Stafford
Journal: BMJ (2009)

Forensic scientist who left West Germany during the cold war to work in East Berlin

There was something different about Professor Otto Prokop. In 1960, when he lectured students in forensic medicine, Berlin’s Charite medical school was in the communist eastern half of Berlin. Many East German scientists were fleeing to West Germany and beyond, but Prokop had moved three years before from West Germany to lead Charite’s Forensic Medicine Institute.

Prokop was not yet 40 years old but already considered one of Europe’s top forensic scientists. He was an exotic sight in bleak and grey East Berlin, dressed in a well tailored business suit, with trademark bow tie, and he had a thick Austrian dialect. 

“He was different,” recalls Gunther Geserick, at the time a 22 year old medical student. “His lectures were fantastic. He was witty, lively, energetic. We were amazed at his encyclopedic knowledge. He was a master of Latin quotations and Greek mythology. His ideas were so original. I was enthralled.”

So enthralled that the young Geserick, who had been aiming towards surgery, switched to forensic medicine. Two years later he joined the institute, becoming Prokop’s protege and then deputy director until Prokop retired in 1987.

During his three decades in East Berlin, Prokop achieved almost …
Spermicides and Birth Defects
Authors: George C. Denniston
Journal: JAMA (1982)

<h3>To the Editor.—</h3> In the article by Jick et al (1981;245:1329), spermicides were implicated in birth defects. I suggest that it is the method of use, and not the spermicides themselves, that may be implicated in the production of birth defects. Many women use spermicides carefully during the days around ovulation, but not so carefully when they think they are "safe." Conceptions are therefore more likely to occur at some less than optimum time. If sperm are deposited in the Fallopian tubes several days before ovulation, they are approaching nonviability when the ovum appears; or if the sperm do not appear in the tubes until 11 hours after ovulation, the ovum is almost gone. Either way, the risk of blighted ova, increased miscarriages, and increased malformations is raised by avoiding the optimum time to conceive. There is ample literature on this point in connection with the use of the rhythm
Pertussis vaccine as immunological adjuvant in leukaemia and lymphoma.
Authors: J G Sinkovics, E Shirato, C C Shullenberger
Journal: BMJ (1970)

culation is indicated by our findingsl 2 that in blood obtained from the uterine veins this factor was greater than that in the arterial blood.Plasminogen activator levels were estimated by the euglobulin lysis time (E.L.T.) method.3Evidence supporting our findings is provided by the observations published by bination of phenformin-stanozolol is as Maki et al.4These workers, investigating the fibrinolytic activity in blood from the vasa efferentia of the uterus and comparing it with that in blood from a cubital vein, found that this activity was considerably increased in the blood from the uterus.They suggested that this constituted indirect evidence that the uterus contributed activators to the systemic circulation.Moreover, in a comparative study of blood from a uterine vein and a uterine artery in 14 patients, Cash,5 using the E.L.T. method, found marked increased fibrinolytic activity in the former.-Iam, etc.,
Quantifying intervention-related improvements in exercise tolerance
Authors: B. J. Whipp, S. A. Ward
Journal: European Respiratory Journal (2009)

Among the benefits expected to result from a therapeutic intervention in patients with impaired systemic functioning is an increase in exercise tolerance. For this a constant high-intensity work rate has been shown to provide a more sensitive index of improvement than the maximum work rate, or oxygen uptake, on a symptom-limited incremental test. However, the extremely large variability of the improvement in this particular index of tolerance undermines the ability to make general inferences for the underlying functional improvement. We argue that this is a necessary consequence of the particular work rate chosen for the test and the change in the parameters of the subject's hyperbolic power–duration relationship for that form of exercise: its “critical power” and “curvature constant”. Without knowledge of these features, any absolute or per cent increase in tolerance time to a single constant-load exercise bout must be interpreted with caution regarding the physiological benefit(s) that have accrued from the intervention.
Teachers abroad: collaboration between the Peace Corps, Seed Global Health, and African medical and nursing schools in faculty scale-up
Authors: Fitzhugh Mullan, Dick Day, Jennifer Goldsmith, Patricia Daoust, Sadath Sayeed, Vanessa B Kerry
Journal: The Lancet Global Health (2014)

BackgroundIn 2012, the US Peace Corps and Seed Global Health, supported by PEPFAR, developed the Global Health Service Partnership (GHSP) to address extreme shortages of health-care providers in low-income countries. In 2013, GHSP placed 30 physicians and nurses on faculties at medical and nursing schools in Tanzania, Uganda, and Malawi to support educational capacity development aimed at long-term health system strengthening. Seed Global Health offers privately funded debt repayment to offset loan obligations and reduces barriers to participation.MethodsGHSP recruited US faculty to work at sites selected in consultation with Ministries of Health and Education and other partners. Qualitative and quantitative surveys of applicants and volunteers were used to identify opportunities for continued and enhanced volunteer support during service.FindingsData review of recruitment and placements identified two career stages of volunteers—early and late. Regardless of seniority, substantial financial challenge exists for individuals considering GHSP. 27 volunteers require debt relief. The bimodal volunteer distribution suggests that, worldwide, opportunities are growing for midcareer faculty to serve as clinical educators. Midcareer faculty will need specific support because they are often unable to consider positions that entail substantial salary reduction associated with a year working abroad or an interruption of their academic activities, or both.InterpretationThe financial challenge to individuals considering global service is problematic, especially for midcareer professionals. A so-called sabbatical corps could provide US institution-based funding and support for faculty who would transfer skills to their global counterparts and bring novel skills home in return. The sabbatical corps would effectively expand the pool of educators needed.FundingPresident's Emergency Plan for AIDS Relief, the Exxon Mobil Foundation, the Engelhard Foundation, Draper Richards Kaplan Foundation, Pfizer Foundation, and Goldman Sachs Gives.
UK major trauma outcome study
Authors: A M Leaman
Journal: BMJ (1992)

incidents jointly with the British Association for Accident and Emergency Medicine.The association organises courses on major incidents, and the five day course on immediate care includes formal training on the same subject.The diploma in immediate medical care of the Royal College of Surgeons of Edinburgh examines candidates on skills gained in these courses.The courses and the diploma are much more relevant to on site medical services at major incidents than the much promoted advanced trauma life support courses, which relate to the care of a single patient by a single doctor in hospital.4We believe that the key issues are, firstly, that the person serving as medical incident officer must be properly trained in managing major incidents and must participate regularly in exercises with colleagues from other services; and, secondly, that members of site medical teams must regularly work outside hospital on the many cases of trauma seen in day to day practice.