tbuckley/cabot-search huggingface dataset:
Circulating Tumor Cells in Patients With Carcinoma
Authors: Marvin M. Romsdahl
Journal: JAMA (1965)

High-molecular-weight dextran and millipore filtration have been successfully utilized for isolation of cancer cells and large hematopoietic elements from blood. Circulating tumor cells were detected in peripheral blood from nine (3.5%) of 255 patients. Regional blood samples were positive for tumor cells in two of 35 cases. Two of 28 patients having local blood examined were found to have tumor cells. A majority of the patients (11 of 13 cases) with detectable tumor cells in the blood had disseminated cancer. No tumor type predominated in yielding circulating cancer cells. The application of current criteria in the diagnosis of circulating tumor cells indicates that their presence is substantially less than previously reported. Immature hematopoietic elements, which require differentiation from malignant cells, are commonly found in the blood of patients with carcinoma.
Statins: underused by those who would benefit
Authors: S. B Hulley
Journal: BMJ (2000)

papers p 983 

The United States Food and Drug Administration has recently rejected proposals by the manufacturers of lovastatin and pravastatin to make these drugs available over the counter. Advisers to the Food and Drug Administration decided that physicians should probably determine who should get the drugs as well as monitoring them for side effects. The main arguments for allowing over the counter sales were summarised in a recent conference sponsored by the industry: statins are effective, easy to take, and relatively safe, and many people who should be taking these drugs are not doing so.1

The underuse of statins is most apparent in the secondary prevention of heart disease in patients with known atherosclerotic disease, for whom there is overwhelming evidence that statins are highly beneficial. 2 3 In one recent survey, for example, only 37% of patients with recent myocardial infarction and blood cholesterol concentrations above 2 g/l had been given drugs to lower their lipid concentrations and few had reached their target cholesterol concentrations.4 Most patients with heart disease have concentrations of low density lipoprotein cholesterol that warrant treatment, and making statins available over the counter might increase their use (as has occurred with aspirin).5

Undertreatment is also a problem for the much larger population …
<i>CLOCK</i> in Breast Tumorigenesis: Genetic, Epigenetic, and Transcriptional Profiling Analyses
Authors: Aaron E. Hoffman, Chun-Hui Yi, Tongzhang Zheng, Richard G. Stevens, Derek Leaderer, Yawei Zhang, Theodore R. Holford, Johnni Hansen, Jennifer Paulson, Yong Zhu
Journal: Cancer Research (2010)

The transcription factors responsible for maintaining circadian rhythm influence a variety of biological processes. Recently, it has been suggested that the core circadian genes may play a role in breast tumorigenesis, possibly by influencing hormone regulation or other pathways relevant to cancer. To evaluate this hypothesis, we conducted a genetic and epigenetic association study, as well as a transcriptional profiling array and a pathway-based network analysis. We report significant correlations between single nucleotide polymorphisms associated with the central circadian regulator CLOCK and breast cancer risk, with apparent effect modification by estrogen receptor/progesterone receptor status. We also found that hypermethylation in the CLOCK promoter reduced the risk of breast cancer, and lower levels of CLOCK expression were documented in healthy controls relative to normal or tumor tissue from patients with breast cancer. Finally, we silenced CLOCK in vitro and performed a whole-genome expression microarray and pathway analysis, which identified a cancer-relevant network of transcripts with altered expression following CLOCK gene knockdown. Our findings support the hypothesis that circadian genes influence tumorigenesis, and identify a set of circadian gene variants as candidate breast cancer susceptibility biomarkers.
Clioquinol inhibits the proteasome and displays preclinical activity in leukemia and myeloma
Authors: X Mao, X Li, R Sprangers, X Wang, A Venugopal, T Wood, Y Zhang, D A Kuntz, E Coe, S Trudel, D Rose, R A Batey, L E Kay, A D Schimmer
Journal: Leukemia (2008)
Points from Letters: Professional Discipline
Authors: G. C. Greig
Journal: BMJ (1971)

The introduction of a fee for home visiting would remove some of the present dis- incentives to the doctor giving this service, and one hopes it would increase the patient's sense of responsibility in this respect.-Iam.etc., R. WANN LeicesterGood Example SIR,-The medical profession should follow the splendid example of senior civil ser- vants, judges, and shipbuilders and announce that no pay increase will be sought during 1971.This may encourage others to follow suit and will help to slow the Gadarene rush towards national finan- cial disaster.
How Many Autopsies?
Authors: Sidney C. Madden
Journal: JAMA (1965)

Autopsies are important to medicine and society in several ways: (1) They are a revelation to the physician—sometimes of the expected, at other times of unanticipated disease. In either event they contribute to the continuing education of the physician. (2) They are essential in the education of medical students. (3) In certain cases appropriate postmortem examinations are necessary for the maintenance of law and justice in society. (4) To determine the major and contributory causes of death with sufficient accuracy, and to discover the trends of these diseases in society, autopsies must be done on large numbers of deaths or at least on epidemiologically valid samples. (5) Research in the broad sense forms a greater or less part of autopsies done for each of the foregoing purposes. And many new discoveries in disease still await the perceptive studies of autopsies, especially those done in conjunction with selected clinical observations. (6)
Pacemaker channel dysfunction in a patient with sinus node disease
Authors: Eric Schulze-Bahr, Axel Neu, Patrick Friederich, U. Benjamin Kaupp, Günter Breithardt, Olaf Pongs, Dirk Isbrandt
Journal: Journal of Clinical Investigation (2003)

The cardiac pacemaker current If is a major determinant of diastolic depolarization in sinus nodal cells and has a key role in heartbeat generation. Therefore, we hypothesized that some forms of “idiopathic” sinus node dysfunction (SND) are related to inherited dysfunctions of cardiac pacemaker ion channels. In a candidate gene approach, a heterozygous 1-bp deletion (1631delC) in exon 5 of the human HCN4 gene was detected in a patient with idiopathic SND. The mutant HCN4 protein (HCN4-573X) had a truncated C-terminus and lacked the cyclic nucleotide–binding domain. COS-7 cells transiently transfected with HCN4-573X cDNA indicated normal intracellular trafficking and membrane integration of HCN4-573X subunits. Patch-clamp experiments showed that HCN4-573X channels mediated If-like currents that were insensitive to increased cellular cAMP levels. Coexpression experiments showed a dominant-negative effect of HCN4-573X subunits on wild-type subunits. These data indicate that the cardiac If channels are functionally expressed but with altered biophysical properties. Taken together, the clinical, genetic, and in vitro data provide a likely explanation for the patient’s sinus bradycardia and the chronotropic incompetence.
Robert Stanley Miller
Authors: J. SINCLAIR
Journal: BMJ (2003)

Former general practitioner Scotland and New Zealand (b 1920; q Glasgow 1950), died from prostate cancer on 15 July 2003.

Stanley Miller took part in one of the most disastrous naval operations of the second world war. He was involved in the bombing and torpedo attack of 30 July 1941 on the Arctic ports of Petsamo (now Pechanga) in Finland and Kirkenes in Norway. Of the 59 British aircraft involved, 15 were shot down, including the Fulmar in which Miller was the observer. Miller subsequently spent three years in a German prisoner of war camp. He went on to a successful career as a family doctor, mainly in the west of Scotland but also in the Highlands and Islands and, for 10 years, in New Zealand. He leaves a wife, Patricia; two children; and seven grandchildren.
Osteosarcoma with Pericardia! Metastases Seen on Bone Scan
Authors: C DOUGLAS PHILLIPS, BRIAN R. J. WILLIAMSON
Journal: Clinical Nuclear Medicine (1987)

Focal uptake of Tc-99m MDP in soft tissues has been described, usually in areas of dystrophic calcification. Osteosarcoma, a childhood bone tumor, directly forms osteoid, both in the primary and metastatic lesions. Tc- 99m MDP is incorporated in tumor osteoid on delayed images and is seen as areas of increased uptake. Although extraosseous activity in metastatic deposits has been reported, this unusual case demonstrates an osteosarcoma with pericardial metastases seen on Tc-99m bone scan and confirmed by CT.
Abstract LB-451: Treatment with hormonal blockade in estrogen receptor-positive tumors and correlation with molecular markers: a phase I pilot study of anastrozole in combination with everolimus, bevacizumab, sorafenib or erlotinib
Authors: Jennifer J. Wheler, Stacy Moulder, Gerald Falchook, Filip Janku, Aung Naing, Siqing Fu, Sarina Piha-Paul, Apostolia Maria Tsimberidou, Razelle Kurzrock
Journal: Cancer Research (2012)

Abstract Background: Estrogen receptors are expressed across a variety of solid tumor types and may predict response to hormonal therapy. Objectives: Objectives were to evaluate safety, response signals and correlation with molecular aberrations. Methods: Beginning December 7, 2010 patients with estrogen receptor positive (ER+), advanced cancers were treated with anastrozole combinations. Toxicities were monitored and imaging evaluations were performed every 3 cycles (1 cycle = 4 weeks). Results: Patients were treated with anastrozole (1 mg) alone or in combination with everolimus (5 or 10 mg PO daily) (N = 18), bevacizumab (10mg/kg or 15 mg/kg IV q21d) (N = 5), sorafenib (200 mg PO BID or 400 mg qam/200 mg qhs) (N = 23), or erlotinib (75 mg PO daily) (N = 3). No dose-limiting toxicities or serious toxicities (≥ grade 3) were observed. On anastrozole/everolimus, 6/18 patients (33%) had either stable disease (SD) ≥ 6 months or partial response (PR) (breast cancer, 4; ovarian cancer, 2). 3 of 4 patients with SD ≥ 6 months or PR and available molecular results showed either PTEN loss or PIK3CA mutation or both. On anastrazole/bevacizumab, 1/5 patients (20%) had SD (11 months+; ovarian cancer). On anastrozole/sorafenib, 23/23 patients had progression of disease (PD). On anastrozole/erlotinib, 3/3 patients had PD. Conclusions: Treatment with anastrozole in combination with everolimus, bevacizumab, sorafenib or erlotinib is feasible and anastrozole/everolimus has demonstrated response signals in ER+ tumors (breast and ovarian), particularly in patients with PTEN loss or PIK3CA mutations. Study expansion and molecular profiling are ongoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-451. doi:1538-7445.AM2012-LB-451
Transient bone marrow oedema in a child
Authors: L Kroger
Journal: Annals of the Rheumatic Diseases (2004)

Transient bone marrow oedema (TBMO) is an uncommon condition associated with joint and bone pain on activity. The most common localisation is the proximal femur, and it mainly affects only one bone.1 Reports of bone marrow oedema in children are scarce.2–4

An 8 year old boy was referred to hospital owing to difficulty in walking. He had started ski jumping 2 weeks earlier, but his history showed no injuries in the extremities. He complained of pain in the knees, ankles, and wrists. Mild fever and signs of upper respiratory tract infection were detected and reactive arthritis was suspected. Treatment with naproxen was started and he was discharged. Ultrasound investigation showed only slight symmetrical oedema in the ankle joints. Haemoglobin, white blood cell count, and thrombocytes were all within normal limits.

During the next 2 weeks, the pain …
HLA Patterns and Disease Associations
Authors: Stephan E. Ritzmann
Journal: JAMA (1976)

The a priori biologic significance of the histocompatibility complex with its excessive polymorphism remains unknown. Teleologically, however, the role of the HLA system may be viewed as vital for survival of the species and the individual by providing the host with a recognition system of and defenses against viruses, microorganisms, parasites, plant antigens, neoplastic cells, and others. HLA testing, in addition to its usefulness in donor selection for transplantation, has been recently applied to the diagnosis and differentiation of specific diseases, the prediction of disease development (risk prediction), and as a basis for prognostic evaluations. An increasing number of diseases is being shown to be linked by specific HLA antigens and certain common denominators, such as arthritides, autoimmune components or infections, suggesting common etiologic or pathogenic mechanisms or both. These diseases with HLA associations can be separated into those that appear certain, probable, or only statistically possible.
Abstract S6-10: Identification of a Novel Tumor Suppressor Network Reveals a Role for Proto-Oncogenic Receptor Tyrosine Kinases in Triple-Negative Breast Cancer
Authors: T Sun, KL Meerbrey, J Kessler, M Botero, I Migliaccio, DX Nguyen, NN Pavlova, RJ Bernardi, E Schmitt, SG Hilsenbeck, CJ Creighton, CA Shaw, R Gibbs, D Wheeler, CK Osborne, R Schiff, SJ Elledge, TF. Westbrook
Journal: Cancer Research (2010)

Abstract Breast cancer is a collection of diseases with distinct clinical behaviors and underlying genetic causes. Triple-negative breast cancer (TNBC) is a common subtype of breast cancer that confers a particularly poor prognosis and is refractory to current targeted therapies. Unfortunately, the molecular determinants driving this aggressive malignancy are poorly understood. Using an unbiased genetic screen, we have identified a novel tumor suppressor network that governs proliferation and transformation of TNBCs in vitro and in vivo. We define SECT21 as a core component in this network and a commonly inactivated tumor suppressor in TNBC. SECT21 is a potent suppressor of human mammary epithelial cell proliferation and transformation. SECT21 function is frequently compromised in human TNBCs by inactivating mutations, deletion, or loss of protein expression. Mechanistically, SECT21 is a tyrosine phosphatase that suppresses cellular transformation by interacting with and inhibiting several oncogenic receptor tyrosine kinases including HER2, EGFR, and PDGFR. Notably, the tumorigenic and metastatic potential of SECT21-deficient TNBCs is severely impaired by restoring SECT21 function or by inhibiting kinase targets of SECT21, suggesting that TNBCs are dependent on the proto-oncogenic tyrosine kinases constrained by SECT21. Collectively, these data identify SECT21 as a commonly inactivated tumor suppressor and provide a rationale for combinatorially targeting tyrosine kinases in TNBC and other cancers based on their profile of tyrosine phosphatase activity. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S6-10.
Type 2 diabetes and hepatocellular carcinoma: A cohort study in high prevalence area of hepatitis virus infection
Authors: Mei‐Shu Lai, Meng‐Shu Hsieh, Yueh‐Hsia Chiu, Tony Hsiu‐Hsi Chen
Journal: Hepatology (2006)

This study aimed to elucidate the relationship of type 2 diabetes, other known risk factors, and primary hepatocellular carcinoma (HCC) in countries with a high prevalence of hepatitis infection. We followed a prospective cohort of 54,979 subjects who participated in the Keelung Community-Based Integrated Screening program between 1999 and 2002. A total of 5,732 subjects with type 2 diabetes cases were identified at enrollment on the basis of fasting blood glucose level, and a total of 138 confirmed HCC cases were identified either through two-stage liver cancer screening or linkage with the National Cancer Registry. The independent effect of type 2 diabetes on the incidence of HCC and the interaction between type 2 diabetes and hepatitis infection or lipids profile were assessed using the Cox proportional hazards regression model. After controlling for age, sex, hepatitis B virus (HBV), hepatitis C virus (HCV), smoking, and alcohol consumption, the association between type 2 diabetes and incidence of HCC (excluding 33 prevalent cases identified at enrollment) was modified by HCV status and cholesterol level. The associations were only statistically significant (adjusted hazard ratio [HR] = 2.08 [1.03-4.18]) for being HCV negative and for having hypercholesterolemia (adjusted HR = 2.81 [1.20-6.55]). These statistically significant findings remained even excluding cases of diabetes newly diagnosed at enrollment. In conclusion, in an area with a high prevalence of hepatitis virus infection, type 2 diabetes increases the risk of developing HCC in those who are HCV negative or have a high level of total cholesterol.
Organ donors' funeral costs should be paid, report says
Authors: N. Hawkes
Journal: BMJ (2011)

Organ donation rates might be boosted if donors’ funeral costs were to be paid by the NHS, the Nuffield Council on Bioethics suggests in a new report.

A payment would be triggered only if donors had signed the organ donor register and died in circumstances making their organs available for donation. The report draws a parallel with existing arrangements for people who donate their bodies to medicals schools, which then undertake to arrange their final disposal by cremation or burial.

The working party responsible for the suggestion said that it is a way of offering a financial inducement with little risk of turning organ donation into a financial transaction. The donor would not gain personally so would be unlikely to sign the organ donor register simply to get a free funeral, especially as only a tiny fraction of those who do sign the register are potential donors at their time of death. And even if potential donors had it in mind to spare their estate or next of kin the cost of …
Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo
Authors: Ying Jin, Stanca A Birlea, Pamela R Fain, Tracey M Ferrara, Songtao Ben, Sheri L Riccardi, Joanne B Cole, Katherine Gowan, Paulene J Holland, Dorothy C Bennett, Rosalie M Luiten, Albert Wolkerstorfer, J P Wietze van der Veen, Anke Hartmann, Saskia Eichner, Gerold Schuler, Nanja van Geel, Jo Lambert, E Helen Kemp, David J Gawkrodger, Anthony P Weetman, Alain Taïeb, Thomas Jouary, Khaled Ezzedine, Margaret R Wallace, Wayne T McCormack, Mauro Picardo, Giovanni Leone, Andreas Overbeck, Nanette B Silverberg, Richard A Spritz
Journal: Nature Genetics (2012)
TCTAP A-192 Model for Assessing Cardiovascular Risk in an Asian Population
Authors: Gyung-Min Park, Seungbong Han, Jung Bok Lee, Seon Ha Kim, Min-Woo Jo, Moo Song Lee, Jung-Min Ahn, Seung-Whan Lee, Young-Hak Kim, Beom-Jun Kim, Jung-Min Koh, Hong-Kyu Kim, Jae Won Choe, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2014)
Whole class ban on substances is needed to control designer drugs, says UN agency
Authors: Z. Kmietowicz
Journal: BMJ (2011)

National governments need to adopt generic bans to control entire groups of substances that can be used to make designer drugs, a United Nations report has said.

According to the 2010 annual report of the International Narcotics Control Board, designer drugs are being produced faster and in growing numbers than ever before and are easily available over the internet. Designer drugs imitate the effects of ecstasy, amphetamines, and cocaine.

Since they appeared in 2007 seizures of designer drugs have been reported in Europe, North America, Japan, Australia, and New Zealand. …
Persistent Salmonella Infection in a Female Carrier for Chronic Granulomatous Disease
Authors: ROBERT C. MOELLERING
Journal: Annals of Internal Medicine (1970)

A female carrier for chronic granulomatous disease of childhood has had persistent systemic infections with Salmonella enteritidis for more than 3 years despite rigorous medical and surgical attempts to eradicate the sepsis. Unusual susceptibility to bacterial infection has not previously been described in carriers of chronic granulomatous disease of childhood, and it is postulated that this patient's persistent infection is due to survival of salmonellae in the macrophages of her reticuloendothelial system, where they are protected from the effects of systemic antibiotics.
SUCTION IN THE TREATMENT OF LARYNGEAL DIPHTHERIA
Authors: HARRY R. LITCHFIELD
Journal: JAMA (1923)

With the introduction of intravenous antitoxin, direct laryngoscopy with swabbing of the larynx, and finally suction, the mortality figures in laryngeal diphtheria have gradually decreased. <h3>HISTORY OF THE RELIEF OF THIS DISEASE</h3> The earliest records of catheterization of the larynx, for cases of inflammatory stenosis, is found in the writings of Hippocrates. Cannulas were carried into the throat along the jaws so that air might be drawn into the lungs. This procedure was practiced until the discovery of tracheotomy by Aschopiadon in the first century B. C. Catheterization was lost sight of until 1780, when it was revived by Chaussier, who proposed the use of a laryngeal tube in the asphyxia of the new-born and to overcome obstruction due to disease. Dissault, in 1801, and many others after him appear to have had some measure of success in the treatment of laryngeal stenosis by this method, particularly in adults; but
Prognosis of Depression Treated by Electric Convulsion Therapy
Authors: H. F. Jarvie
Journal: BMJ (1954)

ISONIAZIDBRDICJfouHAL of patients with a combination of streptomycin and isoniazid to be more effective than treatment with either drug alone, even in the early stages, when development of resistant strains of tubercle bacilli would probably not have occurred.When either streptomycin or isoniazid alone was added to our cultures, in most experiments resistant strains even- tually replaced the sensitive bacilli which had been killed.When the two drugs were added together resistant strains did not emerge.These results are analogous to the observation that a, combination of streptomycin and isoniazid prevents or delays the development of resistant strains in pulmonary tubercuilosis (Medical Research Council, 1953a). SummaryAt concentrations four to eight times those necessary to inhibit growth of tubercle bacilli the bactericidal acti- vities of streptomycin and isoniazid were the same.At concentrations ten times higher, corresponding to maximal serum levels, the activity of streptomycin was greater than that of isoniazid.The activity of the combination of both drugs was higher than that of either alone, and prevented the growth of resistant strains of tubercle bacilli.
Acne and anticonvulsants.
Authors: R Greenwood, P B Fenwick, W J Cunliffe
Journal: BMJ (1983)

The severity of acne and rate of excretion of sebum were assessed in 243 patients with epilepsy taking various anticonvulsants who were in hospital long term and in matched controls derived from a normal population of 2176 people. Neither the prevalence of acne nor the sebum excretion rate significantly increased in the patients compared with the controls or in patients taking phenytoin compared with those not. It is concluded that anticonvulsant treatment does not cause acne.