tbuckley/cabot-search huggingface dataset:
Effect of Nancy Reagan's Mastectomy on Choice of Surgery for Breast Cancer by US Women
Authors: Ann Butler Nattinger
Journal: JAMA (1998)

Context.—While the actions of popular figures are believed to influence the behavior of the general public, including health care decisions, little research has examined such an effect.Objective.—To determine whether a temporal association exists between use of breast-conserving surgery (BCS) for treatment of breast cancer and Nancy Reagan's mastectomy in October 1987.Design/Setting.—Population-based observational cohort study.Patients.—Two sources of data: (1) 82230 women aged 30 years and older who were included in the Surveillance, Epidemiology, and End Results tumor registry because of a diagnosis of local or regional breast cancer from 1983 to 1990; and (2) 80057 female Medicare beneficiaries aged 65 to 79 years who received inpatient surgery for local or regional breast cancer in 1987 or 1988.Main Outcome Measure.—Percentage of use of BCS vs mastectomy over time.Results.—Compared with women undergoing surgery for breast cancer in the third quarter of 1987 (just prior to Mrs Reagan's mastectomy), women were 25% less likely to undergo BCS in the fourth quarter of 1987 (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.66-0.85) and in the first quarter of 1988 (OR, 0.76; 95% CI, 0.67-0.86). In subsequent quarters, the rate returned to the baseline. In multivariate analyses, the decline was significant among white but not nonwhite women. It was most prominent among women aged 50 to 79 years in the central and southern regions of the country, and most sustained among women living in areas with lower levels of income and education.Conclusions.—Celebrity role models can influence decisions about medical care. The influence appears strongest among persons who demographically resemble the celebrity, and those of lower income and educational status.
THE NEW SCIENCE OF MEDICINE.
Authors: NORMAN BRIDGE
Journal: JAMA (1884)

Graduation day is an epoch in the life of a man. To the reflecting mind it is crowded with suggestions for thought, while to many it is full of the romantic and of castles in the air. To all who graduate this thought comes, that the world still has for us subjects for study, which, up to this point, we have been unable to touch. The undergraduate's experience in a medical college is sober and fatiguing. In acquiring the medical degree we have studied the science and art of medicine as represented in certain books; by means of lectures and quizzes, by laboratory exercises and practical work; and by the observation and contact of the sick. So far our work has been one of preparation in a very direct and practical way for a particular present object and for larger ulterior purpose in the labor of life. Necessarily many subjects
Managing drug misuse in general practice.
Authors: L. Rozewicz, W. Caan, A. Johns
Journal: BMJ (1992)

of dose in Procrustean NHS methadone pro- grammes.We believe that the time is right to form a multidisciplinary group to promote the rational, humane, and research validated maintenance treatment for opiate addicts that has been a valu- able and traditional feature of British practice since the Rolleston committee first recommended it in 1926.We invite interested doctors to join us in setting up a British Methadone Maintenance Forum and we hope to establish an annual confer- ence on methadone.
Abstract 1921: The L162V Polymorphism of the PPARA Gene is Associated With Stage C of Heart Failure
Authors: Javier Beaumont, Teresa Arias, Begona Lopez, Guillermo Zalba, Oscar Beloqui, Ignacio Garcia-Bolao, Joaquin Barba, Eduardo de Teresa, Javier Diez
Journal: Circulation (2009)

1921: The L162V Polymorphism of the PPARA Gene is Associated With Stage C of Heart Failure Javier Beaumont; Teresa Arias; Begona Lopez; Guillermo Zalba; Oscar Beloqui; Ignacio Garcia-Bolao; Joaquin Barba; Eduardo de Teresa; Javier Diez 1 Cntr for Applied Med Rsch, Pamplona, Spain 2 Univ Clinic of Navarra, Pamplona, Spain 3 Virgen de la Victoria Univ Hosp, Malaga, Spain 4 Cntr for Applied Med Rsch-Univ Clinic of Navarra, Pamplona, Spain Background: In human heart failure (HF) peroxisome proliferator-activated receptor alpha (PPAR alpha) is downregulated and consequently, the expression of genes involved in fatty acid oxidation repressed. The L162V (rs1800206) is a functional polymorphism of the human PPAR alpha gene (PPARA). In the present study we have investigated whether this polymorphism is associated with the development of stage C of HF. Methods and Results: We analyzed the distribution of the L162V polymorphism in genomic DNA extracted from peripheral blood cells of 233 patients in stage A, 208 patients in stage B, 93 patients in stage C and 63 subjects in stage 0 of HF. The mRNA expression of the PPAR alpha target gene long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) was measured in myocardial biopsies of a subgroup of stages B and C patients. We performed functional studies of the L162V polymorphism in cultured HL-1 cardiomyocytes. The V162 allele was more frequent (P<0.05) in stage C patients than in stages 0, A and B subjects. Patients with the V162 allele exhibited decreased (P<0.05) myocardial LCHAD mRNA expression as compared to L162 homozygote patients. In addition, stage C patients exhibited lower myocardial LCHAD mRNA expression than stage B patients. PPAR alpha transcriptional activity and LCHAD mRNA expression were decreased (P<0.05) in cardiomyocytes transfected with the V162 compared to the L162 polymorphic PPAR alpha cDNA. Conclusions: These findings suggest that the V162 allele of the human PPARA gene can be a new risk factor in the development of overt HF, likely via depressed cardiac PPAR alpha activity.
Abstract 1859: Breast cancer risk:tp53 genotyping in a Nigerian population
Authors: Nancy N. Kasvosve, Jim Fackenthal, Jing Zhang, Olufunmilayo Olopade
Journal: Cancer Research (2010)

Abstract Background: Women of African descent have a lower incidence of breast cancer than other ethnicities but higher mortality rates. Their tumors are characterized by an earlier age of onset, aggressive behavior, poor prognosis, and molecular characteristics of “triple negative” status (i.e. lacking detectable ER, PR, and HER2/neu expression). These characteristics are also typical of tumors carrying somatic TP53 mutations. Experimental evidence has shown that somatic inactivation of the TP53 pathway is necessary for tumor development. Null or strongly hypomorphic TP53 mutations inherited through the germline are associated with a high likelihood of tumorigenesis. Studies on different ethnic populations show inheritance of TP53 variants, especially the R72P polymorphism, to be associated with risk of tumor formation in breast and other tissues. These observations suggest that TP53 gene activity plays a significant role in promoting tumor development in tissues. Hypothesis: As the TP53 R72P polymorphism has been associated with cancer risk in non-African populations, and patients of African ancestry frequently have tumors with TP53 mutation-like characteristics, we hypothesize the R72P variant may be associated with low-penetrance breast cancer risk in a Nigerian/Yoruba population. In addition, this variant may be associated with the triple negative tumor subtype. Methods: The study is a case-control analysis using 213 breast cancer patients and 213 unaffected controls from the University Hospital in Ibadan, Nigeria. The TP53 R72P genotype was determined by direct sequencing of TP53 exon 4, amplified by PCR from peripheral genomic DNA. Chi-square statistical analysis was used to compare frequencies of individual alleles and genotypes in between cases and controls. Results and Conclusions: 130 cases and 207 controls have been genotyped so far. Genotype frequencies for G/G, G/C, and C/C were 21%, 38%, and 41% in cases and 12%, 46% and 42% in the controls, respectively with a p value of 0.11 and an odds ratio of 1.24 at 95% CL. Preliminary results indicate a trend toward risk associated with the G/G genotype, though these results do not yet reach statistical significance. This analysis may provide important clues to the genetic basis of cancer risk and tumor etiology in patients of African ancestry. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1859.
697. Molecular Forms of Feline Immunodeficiency Virus Following Gene Transfer to Airway Epithelia
Authors: Marisa Banasik, Christopher Moressi, Melissa Hickey, Todd Scheetz, Paul McCray
Journal: Molecular Therapy (2006)

We are investigating the nonprimate FIV lentiviral vector for gene transfer applications. Although this vector can integrate in transduced cells, little is known about the fate of FIV vector in host cells after infection. Transgenic DNA can persist as an integrated provirus, but may also persist as episomal DNA, such as 1 or 2-LTR circles, in slowly dividing cell types that are potential targets for gene transfer in tissues such as the airway epithelium. Although persistant gene expression in airway epithelia has been observed following FIV gene transfer, this phenomenon may include gene expression from both integrated and non-integrated episomes. To better understand the nature and composition of viral DNA forms that are present in tranduced host cells, we are using quantitative PCR to contrast the abundance of integrated provirus versus episomal 2- LTR circles. Our preliminary data indicate that in dividing cells 2- LTR circles show a gradual decline over time while the integrated forms persist. To better understand the biology of the process of integration site selection, we begun to map integration events in primary airway epithelial cells as an extension of our previous integration mapping study in HepG2 liver cells. To date, we have mapped 28 integration sites, of which 20 integrations occurred within RefSeq genes (71.4% within a RefSeq transcript). Two integrations occurred within an exon, and the remaining integrations were located in introns. Furthermore, this data is similar to our previous findings for 226 FIV integrations in HepG2 cells, in that the integrations in epithelia occur across the RefSeq gene transcripts. These studies provide an important step in understanding the biology and fate of the FIV vector in host cells.
Reduced thymic maturation but normal effector function of CD8+ T cells in CD8 beta gene-targeted mice.
Authors: W P Fung-Leung, T M Kündig, K Ngo, J Panakos, J De Sousa-Hitzler, E Wang, P S Ohashi, T W Mak, C Y Lau
Journal: The Journal of Experimental Medicine (1994)

CD8 is a cell surface glycoprotein on major histocompatibility complex class I-restricted T cells. Thymocytes and most peripheral T cells express CD8 as heterodimers of CD8 alpha and CD8 beta. The intestinal intraepithelial lymphocytes (IEL), which have been suggested to be generated extrathymically, express CD8 predominantly as homodimers of CD8 alpha. We have generated CD8 beta gene-targeted mice. CD8 alpha+ T cell population in the thymus and in most peripheral lymphoid organs was reduced to 20-30% of that in wild-type littermates. CD8 alpha expression on thymocytes and peripheral T cells also decreased to 44 and 53% of the normal levels, respectively. In contrast, neither the population size nor the CD8 alpha expression level of CD8 alpha+ IEL was reduced. This finding indicates that CD8 beta is important only for thymic-derived CD8+ T cells. The lack of CD8 beta reduces but does not completely abolish thymic maturation of CD8+ T cells. Our result also reveals the role of CD8 beta in regulating CD8 alpha expression on thymic derived T cells. Peripheral T cells in these mice were efficient in cytotoxic activity against lymphocytic choriomeningitis virus and vesicular stomatitis virus, suggesting that CD8 beta is not essential for the effector function of CD8+ T cells.
Volvulus of Giant Sigmoidal Diverticulum
Authors: Ellis L. Silberman
Journal: JAMA (1961)

DIVERTICULOSIS of the colon is a relatively common entity. The frequency as found on barium enema examination varies from 5.2%, according to Rankin and Brown, 1 to 8.2%, according to Willard and Brochus. 6 While diverticula occur throughout the large bowel, by far the most frequent site of involvement is the sigmoid. Of all patients with sigmoidal diverticula, 47% present only sigmoidal diverticula, but the sigmoid is involved in combination with other sites in 95% of cases. 2   While the x-ray diagnosis of colonie diverticula is usually established by use of contrast material which may be administered orally or per rectum, the diagnosis may be made from a plain film of the abdomen. The air-filled diverticula appear in an area of slightly increased soft tissue density within which are multiple, small, rounded lucencies that give a bubbly configuration. This is most commonly seen in the lower midabdomen or in
Decreased cholesteryl ester transfer protein (CETP) mRNA and protein and increased high density lipoprotein following lipopolysaccharide administration in human CETP transgenic mice.
Authors: L Masucci-Magoulas, P Moulin, X C Jiang, H Richardson, A Walsh, J L Breslow, A Tall
Journal: Journal of Clinical Investigation (1995)

The plasma cholesteryl ester transfer protein (CETP) mediates the exchange of HDL cholesteryl esters (CE) and VLDL triglycerides leading to catabolism of HDL. There is some evidence that HDL ameliorates the toxicity of LPS, and LPS is known to influence several enzymes affecting HDL metabolism. Therefore, the effects of LPS on CETP and plasma lipoproteins were examined in human CETP transgenic mice. Administration of LPS to mice expressing a CETP transgene linked to its natural flanking sequences (NFR-CETP Tg) resulted in a rapid marked decrease in hepatic CETP mRNA and plasma CETP concentration. Corticosteroid injection produced a similar decrease in hepatic CETP mRNA and adrenalectomy abolished this response to LPS. LPS caused disproportionate reductions in plasma CETP activity compared to mass, and was found to be a potent inhibitor of CETP activity when added directly to plasma. LPS was injected into mice expressing (A) a human apoA-I transgene, (B) apoA-I and NFR-CETP transgenes, or (C) apoA-I and LPS-inducible metallothionein promoter-driven CETP transgenes, producing (A) minimal changes in HDL cholesterol, (B) decreased plasma CETP and increased HDL cholesterol, and (C) increased plasma CETP and decreased HDL cholesterol. Thus, LPS administration produces a profound decrease in hepatic CETP mRNA, primarily as a result of adrenal corticosteroid release. The decrease in plasma CETP activity after LPS administration may reflect both this effect as well as a direct interaction between CETP and LPS. The decrease of CETP in response to LPS has major effects on HDL levels, and may represent an adaptive response to preserve or increase HDL and thereby modify the response to LPS.
Radiological diagnosis of recurrent colonic carcinoma at the anastomosis
Authors: C. Bartram, J. E. Hale
Journal: Gut (1970)

The barium enemas of 23 cases of end-to-end anastomosis following resection of a colonic carcinoma demonstrated that the normal anastomosis should be smooth, symmetrical, and have a regular mucosal pattern. In contrast the three patients reported with proven recurrent carcinoma at the anastomosis showed irregular asymmetrical filling defects1. As a base line the anastomosis should be investigated with a limited double-contrast enema examination six weeks after operation. Earlier examinations may show irregularity due to incomplete healing.
Changes in myocardial energy metabolism in elective coronary angioplasty
Authors: K. Peuhkurinen, M. Ikaheimo, J. Airaksinen, H. Huikuri, M. Linnaluoto, J. Takkunen
Journal: Cardiovascular Research (1991)

Study objective – The aim was to investigate the effect of coronary angioplasty on myocardial energy metabolism, and to assure the safety of the procedure in patients with coronary heart disease. Design – Before angioplasty a catheter was introduced into the coronary sinus. Blood samples were taken simultaneously from femoral artery and coronary sinus before balloon inflation, upon balloon deflation, and two minutes later, and arteriovenous differences in myocardial substrates, pH, Pco2, oxygen saturation, and adenosine catabolites were determined. Patients – 14 patients with angiographically documented coronary artery disease with lesions in the left coronary artery suitable for elective coronary angioplasty were included in the study. Results – During balloon inflation the positive femoroarterial-coronary sinus difference of lactate turned negative, from 0.21(SEM 0.05) mM to −0.10(0.11) mM, p<0.02. At the same time pH and Pco2 differences increased: from 0.04(0.00) U to 0.07(0.01) U, p<0.01, and from −1.15(0.10) kPa to −1.41(0.10) kPa, p<0.01, respectively. The changes were, however, transient and the arteriovenous differences in these metabolic variables rapidly returned towards preinflation levels after balloon deflation. The femoroarterial-coronary sinus concentration differences in glucose and free fatty acids became positive in coronary angioplasty. The energy state remained good during the procedure as assessed from the negligible net efflux of adenosine and its degradation products. Conclusions – Elective coronary angioplasty can be performed without any persistent derangements in myocardial metabolism, and may in fact lead to improvement of utilisation of some myocardial substrates. Lactate appears to be a more sensitive indicator of short term ischaemia than adenosine degradation products.
Modulation of cell recruitment by anti-inflammatory agents in antigen-induced arthritis
Authors: M J Lopez-Armada
Journal: Annals of the Rheumatic Diseases (2002)

To study the effect of meloxicam (MXC) and diclofenac (DCF) on the recruitment of leucocytes during acute experimental arthritis.Rabbits with antigen-induced arthritis were treated with MXC, DCF, or not treated. After 48 hours, synovial fluid (SF) leucocyte influx and prostaglandin E(2) (PGE(2)) levels were evaluated. Interleukin 8 (IL8) and monocyte chemotactic peptide-1 (MCP-1) expression and synthesis were studied in the inflamed tissues.Arthritic knees showed synovial effusion with a high leucocyte count and PGE(2) concentration, and an increased expression of IL8 and MCP-1. Both non-steroidal anti-inflammatory drugs (NSAIDs) reduced PGE(2) levels and the polymorphonuclear cell (PMN) concentration in SF, while the mononuclear cell (MN) concentration was unchanged in the treated groups in comparison with controls. A definite reduction of IL8 levels was obtained with the treatments, but the drugs did not prevent the up regulation of MCP-1.The effect of these NSAIDs in acute arthritis may be related to the down regulation of IL8 production. The results suggest a differential effect of anti-inflammatory drugs on PMN and MN recruitment to the joint.
Interleukin 1 and interleukin 1 inhibitor production by human macrophages exposed to influenza virus or respiratory syncytial virus. Respiratory syncytial virus is a potent inducer of inhibitor activity.
Authors: N J Roberts, A H Prill, T N Mann
Journal: The Journal of Experimental Medicine (1986)

Respiratory viral infections are commonly associated with altered immune responses, such as proliferative responses to mitogens and antigens. To examine potential mechanisms, we examined production of IL-1 and IL-1 inhibitors by purified human peripheral blood-derived macrophages exposed to influenza virus or respiratory syncytial virus (RSV). IL-1 and IL-1 inhibitor activities in supernatant fluids from macrophages exposed to the viruses 24 h previously were measured using the standard mouse thymocyte comitogen assay. Crude fluids from macrophages exposed to influenza virus contained substantial IL-1 activity, whereas crude fluids from macrophages exposed to RSV contained marked IL-1 inhibitor activity. Assays with gel filtration-separated fractions revealed that both influenza virus and RSV induced production of both IL-1 and IL-1 inhibitors. Neither IL-2 nor IL-2 inhibitor activities were detected. Thus, effects of human macrophage-derived factors on thymocyte proliferation, or potentially on human lymphocyte proliferation, may reflect the total or net activity of multiple composite factors, the balance of which varies according to the challenge. The data raise the possibility that marked production of IL-1 inhibitor activity in response to RSV plays a role in the clinical recurrence of RSV infection despite the absence of clear evidence for antigenic shift or drift of the virus.
The evolution of -adrenergic dysfunction during the induction of canine cobalt cardiomyopathy
Authors: D. V UNVERFERTH, R. H FERTEL, J. THOMAS, C. V LEIER, R. CROSKERY, R. HUNSAKER, M. MILLER, L. GIBB, R. HAMLIN
Journal: Cardiovascular Research (1984)

This study was designed to investigate the changes in the beta adrenergic system during the induction of cobalt cardiomyopathy in dogs. Cobalt sulphate, at a dose of 5 mg·kg−1·day−1 was administered intravenously with a low protein, low thiamine diet to 13 dogs. The percentage change of the left ventricular minor axis with systole by echocardiogram (%ΔD) and dP/dtmax were used to monitor left ventricular function. Noradrenaline (NA) was measured in 24 h urine samples. Left ventricular (LV) free wall biopsies were assayed for noradrenaline (LV-NA), cyclic AMP, cyclic GMP and dopamine beta hydroxylase (LV-DBH). Lymphocytes were assayed for β-receptor density. All dogs were studied at baseline and seven were studied after a midpoint cumulative dose of 60 to 90 mg·kg−1 of cobalt; the remaining six dogs were studied when they were in heart failure and had received more than 110 mg·kg−1. During the induction of heart failure the heart rate rose from 112±6 (X±SE) at baseline to 154±9 at the midpoint and 153±9 (both P<0.05) at the final measurement while the %ΔD fell from 35±2% to 31 ±3% and 23±2% (P<0.05) and dP/dt fell from 333±40 kPa·s−1 at baseline to 254±46 kPa·s−1 (P<0.05) and 207±33 kPa·s−1 (P<0.05). Urinary catecholamines rose significantly during the induction of heart failure while LV-NA fell from 117±27 pg·mg−1 tissue at baseline to 48±8 pg·mg−1 at the midpoint and 47± 15 pg·mg−1 at the final measurement (both P<0.05). The density of peripheral lymphocyte beta receptors also fell significantly while the ratio of myocardial cyclic AMP/cyclic GMP fell from 243 ±56 at baseline to 60± 12 (P<0.01) at the midpoint and 46±8 (P<0.01) at the final measurement. These data indicate that aberrations in beta adrenergic function inhibit vital support mechanisms to the cardiovascular system during heart failure.
DIFFERENCES BETWEEN HS-TROP T AND NT-PROBNP AS PREDICTORS FOR CARDIOVASCULAR OUTCOMES IN PATIENTS WITH PERMANENT ATRIAL FIBRILLATION: DATA FROM THE RACE II STUDY
Authors: Bart Mulder, Dirk van Veldhuisen, Harry J.G.M. Crijns, Hans L. Hillege, Jan G. Tijssen, Marco Alings, Maarten P. van den Berg, Isabelle Van Gelder, Michiel Rienstra
Journal: Journal of the American College of Cardiology (2014)
Database of patients possibly exposed to CJD is proposed
Authors: Andrew Moscrop
Journal: BMJ (2001)

A confidential database has been proposed that would contain details of all patients who may have been exposed to Creutzfeldt-Jakob disease (CJD) through medical procedures.

Proposals were put forward last week in a consultation paper from the CJD incidents panel, a group of experts set up last year by England's chief medical officer. The panel reports to the Spongiform Encephalopathy Advisory Committee and the Advisory Committee on Dangerous Pathogens.

At a press briefing Dr Michael Banner, the panel's chairman, said the database would be used to assess whether people who may have been exposed to …
Enzymatically active fibrils generated by the self-assembly of the ApoA-I fibrillogenic domain functionalized with a catalytic moiety
Authors: Fulvio Guglielmi, Daria M. Monti, Angela Arciello, Silvia Torrassa, Flora Cozzolino, Piero Pucci, Annalisa Relini, Renata Piccoli
Journal: Biomaterials (2008)