tbuckley/cabot-search huggingface dataset:
Immunological treatment of cancer
Authors: A. Green
Journal: BMJ (1969)

MEDIBRITSHRNg peutic range " in seven of these.One patient (No. -9) developed a deep haematoma of the calf after minor injury and transient haematuria.Further, eight patients were eventually restabilized only on a dose of warfarin lower than might have been expected from the original phenindione dosage.Other centres may be considering chang- ing patients from phenindione to warfarin, and it is suggested that the initial mainten- ance dose of warfarin should be less than that normally calculated and that fairly close monitoring of the prothrombin time might be instituted for the first few weeks after the transfer.-Iam, etc.,
Faints, fits, and fatalities from emotion in Shakespeare's characters: survey of the canon
Authors: Kenneth W Heaton
Journal: BMJ (2006)

<b>Objectives</b> To determine how often Shakespeare9s characters faint, fit, or die from extreme emotion; to assess Shakespeare9s uniqueness in this regard; and to examine the plausibility of these dramatised events. <b>Design</b> Line by line search through modern editions of these late 16th and early 17th century works for accounts of characters fainting, fitting, or dying while under strong emotion and for no other apparent reason. <b>Data sources</b> All 39 canonical plays by Shakespeare and his three long narrative poems; 18 similar works by seven of Shakespeare9s best known contemporaries. <b>Results</b> 10 deaths from strong emotion are recorded by Shakespeare (three occur on stage); all are due to grief, typically at the loss of a loved one. All but two of the deaths are in the playwright9s late works. Some deaths are sudden. Another 29 emotion induced deaths are mentioned as possible, but the likelihood of some can be challenged. Transient loss of consciousness is staged or reported in 18 cases (sounding like epilepsy in two) and near fainting in a further 13. Extreme joy is sometimes depicted as a factor in these events. Emotional death and fainting also occur occasionally in works by Shakespeare9s contemporaries. <b>Conclusions</b> These dramatic phenomena are part of the early modern belief system but are also plausible by modern understanding of physiology and disease. They teach us not to underestimate the power of the emotions to disturb bodily functions.
Influence of alteration in preload on the pattern of left ventricular diastolic filling as assessed by Doppler echocardiography in humans.
Authors: M F Stoddard, A C Pearson, M J Kern, J Ratcliff, D G Mrosek, A J Labovitz
Journal: Circulation (1989)

We examined the influence of alterations in preload on pulsed Doppler indexes of left ventricular diastolic function in 50 patients including 12 without cardiovascular disease, 29 with coronary artery disease, and nine with critical aortic stenosis. Micromanometer left ventricular pressure was recorded simultaneously with pulsed Doppler echocardiography of left ventricular inflow and M-mode echocardiography of left ventricular diameter. Chamber stiffness constants, kd and kv, were obtained from the diastolic pressure-diameter and pressure-volume relations, respectively. Relaxation was measured by the isovolumic relaxation time constants, TL and TD, derived from the exponential left ventricular pressure decay and maximum negative dP/dt. In 41 patients after nitroglycerin treatment, left ventricular end-diastolic pressure decreased from 18 +/- 5 to 13 +/- 4 mm Hg (p less than 0.001). The ratio of peak early to peak atrial filling velocities and time-velocity integral ratios decreased from 1.08 +/- 0.57 to 0.90 +/- 0.42 (p less than 0.001) and from 1.77 +/- 0.95 to 1.41 +/- 0.71 (p less than 0.001), respectively. The peak early filling velocity and time-velocity integral decreased from 56.1 +/- 15.7 to 49.9 +/- 14.5 cm/sec (p less than 0.001) and from 7.9 +/- 2.7 to 6.8 +/- 2.8 cm (p less than 0.001), respectively. Relaxation (TL, TD, and maximum negative dP/dt) and chamber stiffness (kd and kv) were not impaired after nitroglycerin administration. In 48 patients after ventriculography, left ventricular end-diastolic pressure increased from 18 +/- 6 to 22 +/- 8 mm Hg (p less than 0.001). The peak early and peak atrial filling velocities increased from 57.4 +/- 15.2 to 68.3 +/- 19.7 cm/sec (p less than 0.001) and from 61.0 +/- 22.7 to 69.4 +/- 23.2 cm/sec (p less than 0.01), respectively. As a result, the ratio of peak early to peak atrial filling velocity was unchanged. However, in the aortic stenosis group, the ratio of peak early to peak atrial filling velocity increased from 0.95 +/- 0.64 to 1.10 +/- 0.72 (p less than 0.02). Relaxation and chamber stiffness were unchanged. Thus, a reduction or increase in preload may induce a diastolic filling pattern that mimics or masks diastolic dysfunction, respectively. Preload conditions need to be accounted for when the status of diastolic function is extrapolated from the pulsed Doppler mitral inflow velocity profile.
Exposure to Cotton Dust and Respiratory Disease-Reply
Authors: Siegfried Heyden
Journal: JAMA (1982)

<h3>In Reply.—</h3> The letter by Beck et al quotes two other letters and an unpublished report to the US Labor Department. Until the latter can be reviewed in detail in a medical journal, there is no way we can evaluate their study. The fact that an earlier article<sup>1</sup>has been "criticized" does not necessarily mean that it has been invalidated. On the contrary, we believe the comments and our responses have clarified and strengthened it. The arguments cannot be summarized here, but the reader is urged to examine the letters referenced and to evaluate this matter personally. Beck et al contend that we have "misinterpreted," "misled," and suggested "wrong conclusions" from the study by Merchant et al regarding the influence of smoking, nonsmoking, and cessation of smoking on byssinosis. Again, we urge the reader to examine the original article and our COMMENTARY. We have since found another article<sup>2</sup>
Abstract 5260: Bortezomib and HDAC inhibitor PCI-24781 combination therapy for neuroblastoma
Authors: Erika A. Currier, Sharon A. Illenye, Takamaru Ashikaga, Pamela J. Lescault, Jeffrey P. Bond, Giselle L. Saulnier Sholler
Journal: Cancer Research (2010)

Abstract Background: Neuroblastoma is an aggressive solid tumor with poor prognosis. Novel therapies are needed to help increase the survival and quality of life for affected children. It has been previously shown that bortezomib results in apoptosis in neuroblastoma both in vitro and in vivo. PCI-24781 is a novel pan-HDAC inhibitor which has been shown to be synergistic with bortezomib in lymphoma models. We hypothesize the combination of bortezomib with PCI-24781 would increase cytotoxicity to neuroblastoma. Methods: Several established neuroblastoma cell lines as well as patient-derived primary neuroblastoma cultures were grown in 96-well plates and treated with bortezomib and PCI-24781, both separately and in combination for 48 hours. Cell viability was assessed by calcein AM assays and IC50's and drug synergy was determined at each cell line tested. mRNA was collected from drug treated cell lines and effects on cell signaling was evaluated using U133 mRNA expression arrays and Ingenuity analysis. Cell lysates prepared from drug treated cells were evaluated by western blot for caspase-3 and PARP cleavage. Nude mice were injected with 107 SMS-KCNR cells subcutaneously in the left flank. Mice were treated with daily doses of either 0.5 mg/kg bortezomib, 12.5 mg/kg PCI-24781, or the combination. Mice tumors were imaged using the IVIS lumina imager twice per week and caliper measurements were also obtained weekly until tumor max was reached. Results: All neuroblastoma cell lines and patient cells tested showed sensitivity to bortezomib and PCI-24781 treatment in calcien AM cell viability assays with IC50's for bortezomib less than 50nM and IC50's for PCI-24781 less than 500nM. The combination of bortezomib and PCI-24781 was more cytotoxic than either drug alone. Cells treated with combined treatment showed an increase in caspase-3 and PARP activity confirming apoptosis. Expression analysis showed differential expression in the Notch and Wnt pathways between drug treated and vehicle treated cells. The xenograft models showed a significant decrease in tumor volume in mice treated with both bortezomib and PCI-24781 when compared to the single agent treatment groups or to the control group. Conclusions: Bortezomib and PCI-24781 inhibit neuroblastoma growth both in vitro and in vivo to a greater extent than either drug alone. The mechanism of action is currently being investigated further but certainly involves caspase-3 mediated apoptosis. This combination therapy appears to be effective and well tolerated in the mouse model and would be a novel therapy for neuroblastoma. 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 5260.
Expression of c-myc, c-Ha-ras1, and c-erbB-2 Proto-oncogenes in Normal and Malignant Human Breast Epithelial Cells
Authors: C. C. Benz, G. K. Scott, G. F. Santos, H. S. Smith
Journal: JNCI Journal of the National Cancer Institute (1989)

Short-term cultures of normal human mammary epithelial cells were used to determine the extent to which c-myc, c-Ha-rasl, and c-erbB-2 proto-oncogenes were expressed in proliferating normal cells. This level of expression was compared with that of primary tumor cells, malignant effusion cells, or permanently established breast cancer cell lines. Pure preparations of epithelial organoids from seven different reduction mammoplasty tissue samples yielded proliferating normal epithelial cells upon short-term tissue culture. In every sample, proto-oncogene transcript levels increased upon short-term culture of the epithelial cells. These levels often exceeded by 10-fold the levels measured in uncultured organoids from the same tissue. In four of the seven cultured normal breast samples, at least one of the proto-oncogenes increased its expression to a level equaling or exceeding that found in a proliferating breast cancer cell line, MCF7. One effusion metastasis sample and two primary ductal adenocarcinomas were also examined for proto-oncogene expression. The effusion metastasis sample expressed high levels of c-erbB-2 messenger RNA, in accord with its amplified gene copy number; otherwise, the levels of proto-oncogene transcripts were low in unprocessed tumor and uncultured organoids, but they increased with proliferation of the tumor cells in culture. These results indicate that the variable expression of these proto-oncogenes observed in breast biopsy specimens needs to be controlled for cellular growth rate or proliferation index. Furthermore, these findings suggest that dysregulated proto-oncogene expression, rather than over expression per se, needs to be evaluated as a possible mechanism contributing to the development of human breast cancer. [J Natl Cancer Inst 81:1704–1709, 1989]
Can myocardial contrast echo determine coronary flow reserve?
Authors: F. J T. Cate, P. R Silverman, L. M A Sassen, P. D Verdouw
Journal: Cardiovascular Research (1992)

The aim was to evaluate the applicability of myocardial contrast echocardiography in the measurement of coronary flow reserve.Eleven anaesthetised open chest pigs were studied, in which coronary atherosclerosis had been induced by abrasion of the left anterior descending coronary artery at one month, followed by an atherogenic diet for eight months. Coronary flow reserve was determined by electromagnetic flow measurement and contrast echocardiography before and after partial occlusion of the left anterior descending coronary artery, using papaverine as a coronary vasodilator. Coronary blood flow was reduced by tightening a clamp placed around the coronary artery. Systemic haemodynamics and myocardial wall thickness (epicardial ultrasound 5 MHz transducer) were recorded simultaneously. Echocardiograms were recorded on VHS tape and analysed by digitised videodensitometry off line for construction of the time v videointensity curve (time-intensity curves). From these curves washout time (T50), area under the curve, peak contrast intensity, and time to peak intensity were calculated.Following papaverine, coronary blood flow increased significantly from 47 (SD 23) ml.min-1 at baseline to 88(39) ml.min-1 (p less than 0.05). During the stenosis, flow decreased to 19(16) ml.min-1 (p less than 0.01), and increased to 38(29) ml.min-1 (p less than 0.05 v stenosis) after administration of papaverine. Correlations between coronary blood flow and indices calculated from the quantitative videodensitometric analysis were poor, varying between r = 0.03 for area at control flow to r = 0.62 for T50 during stenosis. The same was true for coronary flow reserve: r = 0.09 for peak to r = 0.75 (p less than 0.05) for time to peak without the stenosis.Current limitations in injection, imaging, and analysis techniques cause variability in data from time-intensity curves, which precludes accurate quantification of coronary flow (reserve) by myocardial contrast echocardiography.
Visualized Renal Pelves With Tc-99m-N-Pyridoxyl-5-Methyltryptophan
Authors: NAOYUKI WATANABE, TETSUO NAKAJIMA, KEIGO ENDO
Journal: Clinical Nuclear Medicine (1996)

The renal pelves are visualized on hepatobiliary scans with Tc-99m dimethyl-iminodiacetate (Tc-99m HIDA). Urinary excretion of Tc-99m-N-pyridoxyl-5-methyltryp-tophan (Tc-99m PMT) is very low compared to Tc-99m HIDA. However, the renal pelves may occasionally be seen on hepatobiliary imaging with Tc-99m PMT. This may be confused with a functioning gall bladder.
Multicenter trial for long-term safety and efficacy comparison of 0.05% desonide and 1% hydrocortisone ointments in the treatment of atopic dermatitis in pediatric patients
Authors: Joseph Jorizzo, Moise Levy, Anne Lucky, Joel Shavin, Gerald Goldberg, Frank Dunlap, Ann Hinds, Laura Strelka, Michael Baker, Michael Tuley, Janusz M Czernielewski
Journal: Journal of the American Academy of Dermatology (1995)
Challenges of infectious diseases in the USA
Authors: Rima F Khabbaz, Robin R Moseley, Riley J Steiner, Alexandra M Levitt, Beth P Bell
Journal: The Lancet (2014)

In the USA, infectious diseases continue to exact a substantial toll on health and health-care resources. Endemic diseases such as chronic hepatitis, HIV, and other sexually transmitted infections affect millions of individuals and widen health disparities. Additional concerns include health-care-associated and foodborne infections--both of which have been targets of broad prevention efforts, with success in some areas, yet major challenges remain. Although substantial progress in reduction of the burden of vaccine-preventable diseases has been made, continued cases and outbreaks of these diseases persist, driven by various contributing factors. Worldwide, emerging and reemerging infections continue to challenge prevention and control strategies while the growing problem of antimicrobial resistance needs urgent action. An important priority for control of infectious disease is to ensure that scientific and technological advances in molecular diagnostics and bioinformatics are well integrated into public health. Broad and diverse partnerships across governments, health care, academia, and industry, and with the public, are essential to effectively reduce the burden of infectious diseases.
Disseminated Herpes Simplex in a Newborn
Authors: Albert W. Hudson
Journal: JAMA (1969)

A subclinical genital infection in the mother was the source of virus in a disseminated, neonatal herpetic infection. Chronic, asymptomatic herpesvirus infection of the female genital tract, as a reservoir of infection, should be diagnosed before the time of delivery in order to prevent exposure of the fetus during passage through the birth canal.
Radiosensitization by Antisense Anti-MDM2 Mixed-Backbone Oligonucleotide in <b> <i>in Vitro</i> </b> and <b> <i>in Vivo</i> </b> Human Cancer Models
Authors: Zhuo Zhang, Hui Wang, Gautam Prasad, Mao Li, Dong Yu, James A. Bonner, Sudhir Agrawal, Ruiwen Zhang
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The MDM2 oncogene, amplified or overexpressed in many human cancers, has been suggested to be a novel target for cancer therapy. We have demonstrated a second-generation antisense antihuman-MDM2 oligonucleotide to have antitumor activity when administered alone or in combination with cancer chemotherapeutic agents. In the present study, we investigated the effect of the antisense oligonucleotide on radiation therapy. Experimental Design: The in vitro radiosensitization activity was determined in cell lines of human cancers of prostate (LNCaP and PC3), breast (MCF-7 and MDA-MB-468), pancreas (PANC-1), and glioma (U87-MG and A172) and its in vivo radiosensitization activity in xenograft models of LNCaP, PC3, MCF-7, MDA-MB-468, and PANC-1. Results: In cells containing at least one functional p53 allele (LNCaP, U87-MG, and A172), after specific inhibition of MDM2 expression, p53 and p21 levels were elevated. In LNCaP cells, the Bax level was increased, and Bcl-2 and E2F1 levels were decreased. In PC3 cells that are p53 null, after inhibition of MDM2 expression, Bax and p21 levels were elevated, and E2F1 levels were decreased. On the basis of in vitro clonogenic assay, the antisense oligonucleotide, in a sequence-specific manner, significantly increased radiation-induced antiproliferation effects. It also increased radiation-induced inhibitory effects on tumor growth in SCID or nude mice bearing LNCaP, PC3, MCF-7, MDA-MB-468, and PANC-1 xenografts. Conclusions: These results suggest that MDM2 has a role in radiation therapy of human cancers, regardless of p53 status, providing a basis for future development of MDM2 inhibitors, such as antisense oligonucleotides, as radiosensitizers.
Does This Patient Have Hypertension?
Authors: Richard A. Reeves
Journal: JAMA (1995)

<h3>CLINICAL SCENARIO</h3><h3>Is This Patient's Blood Pressure Really Elevated?</h3> A 46-year-old man who has recently moved to your neighborhood presents with a painful ankle sprain. Before he leaves, you decide to check his blood pressure (BP) and obtain an initial reading of 164/102mm Hg. He denies having high BP previously. <h3>WHY IS ACCURATE BP MEASUREMENT IMPORTANT?</h3> Elevated arterial BP, or hypertension, is important because it is common, it is clinically silent, it leads to cardiovascular disease (CVD), and it decreases life expectancy. Because surveys find that approximately 20%<sup>1-3</sup>of North American adults have an elevated BP (systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg) or are taking antihypertensive medication, physicians are advised to check all patients periodically for BP elevation.<sup>3-7</sup>On the other hand, overestimation of BP can erroneously label people as hypertensive and potentially result in unnecessary dietary restrictions, exposure to potential side effects
The Unclampable Ascending Aorta in Coronary Artery Bypass Patients
Authors: Mario Gaudino, Franco Glieca, Francesco Alessandrini, Nicola Luciani, Carlo Cellini, Claudio Pragliola, Gianfederico Possati
Journal: Circulation (2000)

Background —The unclampable ascending aorta (UAA) is a condition increasingly encountered during CABG procedures. We report our experience with CABG patients with UAA and place particular emphasis on the preoperative diagnosis and surgical management. Methods and Results —UAA was diagnosed in 211 of 4812 consecutive CABG patients (4.3%). On the basis of the chest radiograph, echocardiogram, and coronary angiograph, a preoperative diagnosis was achieved in only 58 patients (27.4%). An age of &gt;70 years, diabetes, smoking, unstable angina, diffuse coronaropathy, and peripheral vasculopathy were all predictors of UAA. Patients were treated with hypothermic ventricular fibrillation (no-touch technique n=129) or beating heart revascularization (no-pump technique n=82) depending on the possibility of founding an arterial cannulation site. The overall in-hospital mortality rate was 2.8% (6 of 211) with no differences between the 2 surgical strategies. The no-touch technique was associated with a greater incidence of neurological complications (stroke and transient ischemic attack), renal insufficiency, and stay in the intensive care unit and hospital. However, at midterm follow-up, more patients of the no-pump group had ischemia recurrence. Conclusions —A preoperative diagnosis of UAA is achievable only in a minority of patients, which highlights the necessity revising the current diagnostic protocols. The use of the no-touch technique is associated with an high perioperative risk but a superior possibility of complete revascularization, whereas adoption of the no-pump strategy ensures a smoother postoperative course at the expense of an higher incidence of ischemia recurrence.
Antigliadin IgE – indicator of wheat allergy in atopic dermatitis
Authors: E. Varjonen, E. Vainio, K. Kalimo
Journal: Allergy (2000)

Cereal grains are recognized as the cause of adverse reactions in some patients exposed to grain or flour by either inhalation or ingestion. Cereal-related diseases, such as celiac disease and baker's asthma, have been well studied and the causative cereal proteins have been characterized. Although cereals form an essential part of daily nutrition, the allergenic proteins causing symptoms on ingestion in atopic dermatitis (AD) have remained obscure. In this study, we have investigated the allergenic fraction of wheat in AD.Skin prick tests (SPT) with a NaCl wheat suspension and the ethanol-soluble wheat gliadin were performed on 18 wheat-challenge-positive or -negative children with AD, six adult AD patients with suspected cereal allergy, and one adult with wheat-dependent exercise-induced urticaria/anaphylaxis. Serum total IgE and specific IgE-antibody levels to wheat and gluten were measured with the radioallergosorbent test (RAST) simultaneously. In addition serum samples of all 25 patients were analyzed by IgE immunoblotting with the ethanol-soluble wheat-protein extract.Thirteen of the AD children were wheat-challenge-positive, 11/12 of them appeared to be positive with gliadin SPT, and all had an elevated gluten RAST value. Those challenge-negative were negative with both gliadin SPT and gluten RAST. Positive wheat SPT and RAST alone were not associated with positive challenges. Four of the adult patients responded to a cereal-free diet, although only two of them appeared to be positive with gliadin SPT and gluten RAST. A broad and intensive staining of gliadin peptides in IgE-immunoblotting studies was seen in challenge-positive children with positive gliadin SPT and/ or gluten RAST. Besides staining of peptides in the main gliadin area of 30-46 kDa, a characteristic finding was the staining of small, <14-kDa proteins with sera of challenge- and gliadin-SPT-positive patients.We found that wheat-allergic AD patients have IgE antibodies against gliadin that can be detected by both SPT and the sensitive immunoblotting method. This suggests that gliadin peptides are important allergens, and ingestion of wheat causes symptoms of AD. A broad and intensive IgE staining was seen of gliadin peptides against both the previously characterized peptides in the main gliadin area and small, previously uncharacterized peptides of less than 14 kDa. The gliadin SPT and gluten RAST are good screening methods. Further characterization of the IgE-stained gliadin proteins is needed.