tbuckley/cabot-search huggingface dataset:
INDUSTRIAL MEDICAL ASPECTS OF CHEST DISEASES OF OCCUPATIONAL ORIGIN
Authors: Frank Princi
Journal: JAMA (1952)

This discussion is concerned with the management of that patient or groups of patients on whom the label of a pulmonary dust disease has been placed either by the family physician or by a consulting chest specialist. From the narrower viewpoint, it is the classification that has been applied to those persons who are referred to our office for evaluation and treatment. Such patients may or may not have true pulmonary fibrosis, but they always present symptoms that, in one fashion or another, are referable to pulmonary disability. These considerations make it important that all the factors that have contributed to the disease process and the subsequent disability be studied as objectively as possible with whatever tools and disciplines are available. <h3>DIAGNOSTIC CONSIDERATIONS</h3> The diagnosis of pulmonary dust disease, as of any other occupational disease, implies that injury has been sustained in and because of the working environment and that
Novel cutaneous effects of combination chemotherapy with BRAF and MEK inhibitors: a report of two cases
Authors: J.S. Green, D.A. Norris, J. Wisell
Journal: British Journal of Dermatology (2013)

The discovery that some melanoma tumours harbour mutations in the BRAF gene (e.g. V600E) and the subsequent development of specific BRAF inhibitors have greatly improved the treatment of metastatic melanoma. Resistance of tumour cells to BRAF inhibitors is reduced by the addition of an MEK inhibitor; both BRAF and MEK inhibitors have been reported to produce a variety of dermatological toxic effects. Benign naevi often harbour BRAF mutations but few reports exist that document the response of naevus cells to BRAF inhibition. We report sarcoidal-type granulomatous inflammation in two patients with metastatic melanoma undergoing treatment with combination BRAF and MEK inhibitor therapy. This inflammation manifested in one patient as a nonspecific papular eruption; in the other, in association with clinical regression of multiple benign-appearing naevi during the course of therapy. The significance of sarcoidal-type inflammation occurring during treatment of metastatic melanoma with a combination of BRAF and MEK inhibitors is unclear. Its association with the clinical regression of benign-appearing naevi suggests a possible exaggerated inflammatory response to degenerating naevus cells in these lesions.
Absorption and distribution kinetics of the major Parietaria judaica allergen (Par j 1) administered by noninjectable routes in healthy human beings☆☆☆★
Authors: M Bagnasco, G Mariani, G Passalacqua, C Motta, M Bartolomei, P Falagiani, G Mistrello, G W Canonica
Journal: Journal of Allergy and Clinical Immunology (1997)
Common bile duct stone removal with overtube-assisted direct peroral cholangioscopy, without balloon inflation, using an ultra-slim gastroscope following electrohydraulic lithotripsy
Authors: V. Prachayakul, P. Aswakul, U. Kachintorn
Journal: Endoscopy (2011)

We report a case of a 60-year-old woman who presented with obstructive jaundice due to a large (2.5 cm) stone in the common bile duct (CBD). We attempted mechanical lithotripsy but the stone was too big for the basket ([Fig. 1]). We decided to break the stone with electrohydraulic lithotripsy (EHL) and carry out direct peroral cholangioscopy instead of mother-baby endoscopy. In our experience, the mother-baby endoscopic system has several disadvantages. The caliber of the working channel is too narrow and it requires two experienced endoscopists for carrying out the procedure. In addition, the baby endoscope is rather fragile and we have had to very often send it back to the company for repair. Therefore, overtube-assisted direct peroral cholangioscopy using an ultra-slim gastroscope was the preferred intervention in this patient. Before the procedure, we made a hole at 70 cm from the distal end of the overtube of a single-balloon enteroscope (ST-SB1, Olympus, Tokyo, Japan) [1] [2] ([Fig. 2]). Then, an ultra-slim gastroscope (GIF-N260; Olympus, Tokyo, Japan) with a 2-mm working channel and 5.9-mm outer diameter was inserted through the hole. In the next step, first the CBD was cannulated with a duodenoscope using a sphincterotome and 0.035-inch jag wire, and then the duodenoscope was replaced with the ultra-slim gastroscope with the overtube over the wire. The overtube was advanced over the scope into the antrum. The overtube was useful for keeping the endoscope straight when inserted in the stomach as it prevented loop formation during advancement of the scope at a more accessible angle to the papilla. Then, without balloon inflation, the gastroscope was supported by the overtube and advanced over the wire into the bile duct ([Fig. 3]). The CBD stone was visualized ([Fig. 4]) and EHL was carried out to break the stone into several pieces. The stone fragments were removed using a Dormia basket and balloon retrieval catheter ([Fig. 5]). Finally, an occluded cholangiogram showed no residual CBD stones after the procedure.
A New Chair Support for Flexible Endoscopes
Authors: E. Frimberger
Journal: Endoscopy (1977)

A new chair support for flexible endoscopes simplifies sigmoidoscopic endoscopy. The endoscopist sits on a stool with a moveable support for the endoscope. This allows working without much fatigue and the endoscopist can insert and move the endoscope himself. We examined 50 patients in the described technique. We reached an average depth of intubation of 45-50 cm and the average examination took less than 5 minutes.
A Multicenter, Phase 2 Study of Vascular Endothelial Growth Factor Trap (Aflibercept) in Platinum- and Erlotinib-Resistant Adenocarcinoma of the Lung
Authors: Natasha B. Leighl, Luis E. Raez, Benjamin Besse, Peter J. Rosen, Fabrice Barlesi, E. Massarelli, Nashat Gabrail, Lowell L. Hart, Kathy S. Albain, Lloyd Berkowitz, Ostap Melnyk, Frances A. Shepherd, Lars Sternas, Judie Ackerman, Zhenming Shun, Vincent A. Miller, Roy S. Herbst
Journal: Journal of Thoracic Oncology (2010)
Bitemporal Visual Field Loss in Presumed Multiple Sclerosis
Authors: Bennet Lavenstein
Journal: JAMA (1976)

<h3>To the Editor.—</h3> The article by Drs Sacks and Melen (234:69, 1975) was enlightening in view of the rare occurrence of simultaneous bitemporal field defects in multiple sclerosis; however, the implications of ascribing this type of field loss to only a presumed diagnosis of multiple sclerosis in a patient so affected may be misleading and should be cautioned against. Multiple sclerosis does not protect the nervous system from other insults. Slow-growing meningiomas, parasellar cysts, intrasellar and extrasellar tumors, or aneurysmal dilation of the supraclinoid portion of the carotid artery have all been associated with the chiasmal syndrome thereby resulting in subtle, unrecognized visual field loss. Granted that lesion spread in time and space in the nervous system suggests multiple sclerosis, one could become concerned about attributing the sudden development of bitemporal visual field loss to multiple sclerosis alone. Certainly, with the knowledge gained from noninvasive neuroradiological procedures such as sodium
Intellectual conformism depends on institutional incentives, not on socialized culture
Authors: Li Bennich-Björkman
Journal: Behavioral and Brain Sciences (2006)

The study by Ceci et al. shows that academic behavior associated with the core principles of intellectual freedom is more shaped by institutional incentives than by organizational culture. From an organizational theoretical point of view, this is quite an unexpected finding, not least because we do believe universities to be fairly strong and explicit cultures that should be successful in socialization.
A PAPER THAT CHANGED MY PRACTICE
Authors: J. Dunn
Journal: BMJ (1996)

Most patients are not manipulative but those who are can produce strong feelings of anger and hostility in doctors who treat them. George Murphy and Samuel Guze's paper, “Setting limits: the management of the manipulative patient,” is the perfect antidote.1 If you can suspend your prejudices against the facts that the authors are psychotherapists and that they wrote the article at the dawn of the permissive era you will be rewarded with a completely jargon free, well written, and commonsense guide on how to recognise and manage manipulative patients.

The examples used …
Human Ro60 (SSA2) genomic organization and sequence alterations, examined in cutaneous lupus erythematosus
Authors: T.P. Millard, G.H.S. Ashton, E. Kondeatis, R.W. Vaughan, G.R.V. Hughes, M.A. Khamashta, J.L.M. Hawk, J.M. Mcgregor, J.A. Mcgrath
Journal: British Journal of Dermatology (2002)

The Ro 60 kDa protein (Ro60 or SSA2) is the major component of the Ro ribonucleoprotein (Ro RNP) complex, to which an immune response is a specific feature of several autoimmune diseases. The genomic organization and any sequence variation within the DNA encoding Ro60 are unknown.To characterize the Ro60 gene structure and to assess whether any sequence alterations might be associated with serum anti-Ro antibody in subacute cutaneous lupus erythematosus (SCLE), thus potentially providing new insight into disease pathogenesis.The cDNA sequence for Ro60 was obtained from the NCBI database and used for a BLAST search for a clone containing the entire genomic sequence. The intron-exon borders were confirmed by designing intronic primer pairs to flank each exon, which were then used to amplify genomic DNA for automated sequencing from 36 caucasian patients with SCLE (anti-Ro positive) and 49 with discoid LE (DLE, anti-Ro negative), in addition to 36 healthy caucasian controls.Heteroduplex analysis of polymerase chain reaction (PCR) products from patients and controls spanning all Ro60 exons (1-8) revealed a common bandshift in the PCR products spanning exon 7. Sequencing of the corresponding PCR products demonstrated an A > G substitution at nucleotide position 1318-7, within the consensus acceptor splice site of exon 7 (GenBank XM001901). The allele frequencies were major allele A (0.71) and minor allele G (0.29) in 72 control chromosomes, with no significant differences found between SCLE patients, DLE patients and controls.The genomic organization of the DNA encoding the Ro60 protein is described, including a common polymorphism within the consensus acceptor splice site of exon 7. Our delineation of a strategy for the genomic amplification of Ro60 forms a basis for further examination of the pathological functions of the Ro RNP in autoimmune disease.
Carotid arteriosclerosis in identical twins discordant for cigarette smoking.
Authors: A Haapanen, M Koskenvuo, J Kaprio, Y A Kesäniemi, K Heikkilä
Journal: Circulation (1989)

From a nationwide twin panel, identical twin pairs with highest discordance in cigarette smoking were selected for a study of arteriosclerosis (49 pairs with a mean age of 52 years). Smoking history was obtained in 1975, 1981, and 1986. The mean life-long smoking dose of the smoking cotwins was 20 package-years. The smoking and nonsmoking cotwins had similar systolic and diastolic blood pressures, total plasma cholesterol level, body mass index, and some psychosocial factors; the only difference was found in use of alcohol, which was greater among smoking cotwins. Duplex sonography of carotid arteries was performed. Carotid artery stenoses (narrowing of area of the lumen with 15-60%) were found in nine pairs: in nine smoking twins and in two of their nonsmoking cotwins (p = 0.036). The total area of carotid plaques was 3.2 times larger in smoking cotwins (p less than 0.001). The thickness of the inner layer of carotid arteries was more marked in smoking cotwins (p less than 0.001). The size of plaques and the degree of inner layer thickening correlated with the dose of smoking (NS). The association of smoking with carotid arteriosclerosis was highly significant even after the adjustment for age, total plasma cholesterol level, diastolic blood pressure, and body mass index in multiple logistic regression analyses.
When Most Doctors Are Women: What Lies Ahead?
Authors: Wendy Levinson, Nicole Lurie
Journal: Annals of Internal Medicine (2004)

The profession of medicine is becoming feminized: The number of women enrolled in medical school and residency programs has increased dramatically over the past several decades. Some researchers have examined how women are faring in the profession, but few have considered how feminization of the profession will affect patient care and health care systems, as well as the profession itself. We predict that notable changes may emerge in 4 domains: the patient–physician relationship, the local delivery of care, the societal delivery of care, and the medical profession itself. We also consider the potential positive and negative consequences of a predominantly female physician workforce on these domains.
Identification of Protein Cofactors Necessary for Sequence-specific Plasmid DNA Nuclear Import
Authors: Aaron M Miller, Felix M Munkonge, Eric WFW Alton, David A Dean
Journal: Molecular Therapy (2009)

Although transfections are routinely used in the laboratory, the mechanism(s) by which exogenous DNA is transported into the nucleus is poorly understood. By improving our understanding of how vectors circumvent the numerous cellular barriers to gene transfer, more efficient gene delivery methods can be devised. We have begun to design plasmid constructs that enter the nucleus of specific cell types in the absence of cell division, thereby enhancing levels of expression. We have shown that inclusion of specific DNA sequences in plasmid constructs mediates nuclear import both in vitro and in vivo. Here, we use plasmid affinity chromatography, mass spectrometry (MS), and live-cell pulldowns of transfected plasmid constructs to identify protein cofactors that interact in a sequence-specific manner with these DNA nuclear targeting sequences (DTSs). Importin β1, importin 7, and the small guanosine triphosphatase Ran all demonstrate DTS-specific interaction in both MS and pull-down assays, consistent with our model of plasmid nuclear import. In addition, knockdown of importin β1 with small interfering RNA (siRNA) abrogates plasmid nuclear import, indicating that it is a necessary cofactor. Our discovery that specific karyopherins mediate plasmid nuclear import can be used to design more effective vectors for gene delivery. Although transfections are routinely used in the laboratory, the mechanism(s) by which exogenous DNA is transported into the nucleus is poorly understood. By improving our understanding of how vectors circumvent the numerous cellular barriers to gene transfer, more efficient gene delivery methods can be devised. We have begun to design plasmid constructs that enter the nucleus of specific cell types in the absence of cell division, thereby enhancing levels of expression. We have shown that inclusion of specific DNA sequences in plasmid constructs mediates nuclear import both in vitro and in vivo. Here, we use plasmid affinity chromatography, mass spectrometry (MS), and live-cell pulldowns of transfected plasmid constructs to identify protein cofactors that interact in a sequence-specific manner with these DNA nuclear targeting sequences (DTSs). Importin β1, importin 7, and the small guanosine triphosphatase Ran all demonstrate DTS-specific interaction in both MS and pull-down assays, consistent with our model of plasmid nuclear import. In addition, knockdown of importin β1 with small interfering RNA (siRNA) abrogates plasmid nuclear import, indicating that it is a necessary cofactor. Our discovery that specific karyopherins mediate plasmid nuclear import can be used to design more effective vectors for gene delivery.
Use of Enalapril To Attenuate Decline in Renal Function in Normotensive, Normoalbuminuric Patients with Type 2 Diabetes Mellitus
Authors: Mordchai Ravid
Journal: Annals of Internal Medicine (1998)

Background: Angiotensin-converting enzyme (ACE) inhibitors attenuate the decline in renal function in diabetic patients with microalbuminuria. However, no data are available on the use of ACE inhibitors to prevent the decrease in renal function in normotensive, normoalbuminuric patients with type 2 diabetes. Objective: To evaluate the effect of prolonged ACE inhibition on renal function and albuminuria in patients with type 2 diabetes. Design: Randomized, double-blind, placebo-controlled trial with 6-year follow-up. Setting: Eight outpatient clinics coordinated by a department of medicine in a university hospital. Patients: 156 patients in whom type 2 diabetes was diagnosed after 40 years of age who had a baseline mean blood pressure less than 107 mm Hg and albuminuria (albumin excretion ≤ 30 mg/24 h). Intervention: Enalapril, 10 mg/d, or placebo. Measurements: Degree of albuminuria at 24 hours, creatinine clearance, blood pressure, and hemoglobin A1C values. Results: Enalapril therapy decreased albumin excretion from a mean ±SD of 11.6 ± 7 mg/24 h to 9.7 ± 6 mg/24 h at 2 years. This was followed by a gradual increase to 15.8 ± 8 mg/24 h at 6 years. In the placebo group, albumin excretion increased from 10.8 ± 8 mg/24 h to 26.5 ± 10 mg/24 h at 6 years (P = 0.001 for enalapril compared with placebo). Transition to microalbuminuria occurred in 15 of 79 (19%) placebo recipients and 5 of 77 (6.5%) enalapril recipients. Enalapril treatment resulted in an absolute risk reduction of 12.5% (95% CI, 2% to 23%; P = 0.042) for development of microalbuminuria. After 6 years, creatinine clearance decreased from 1.78 ± 0.13 mL/s to 1.63 ± 0.12 mL/s (mean decrease, 0.025 mL/s per year) in enalapril recipients and from 1.81 ± 0.15 mL/s to 1.57 ± 0.17 mL/s (mean decrease, 0.04 mL/s per year) in placebo recipients (P = 0.040). Hemoglobin A1C values decreased modestly in both groups. Mean blood pressure remained normal (<107 mm Hg) in all patients. Conclusions: Enalapril attenuated the decline in renal function and reduced the extent of albuminuria in normotensive, normoalbuminuric patients with type 2 diabetes. Further research is needed to determine whether this treatment forestalls the development of overt nephropathy.
A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia
Authors: Suk-Kyun Yang, Myunghee Hong, Jiwon Baek, Hyunchul Choi, Wanting Zhao, Yusun Jung, Talin Haritunians, Byong Duk Ye, Kyung-Jo Kim, Sang Hyoung Park, Soo-Kyung Park, Dong-Hoon Yang, Marla Dubinsky, Inchul Lee, Dermot P B McGovern, Jianjun Liu, Kyuyoung Song
Journal: Nature Genetics (2014)
The Need to Treat Mild Hypertension
Authors: John D. Abernethy
Journal: JAMA (1986)

Despite the clear-cut result of the Australian Therapeutic Trial in Mild Hypertension, which demonstrated prospectively the benefit of treatment of diastolic blood pressure in the range of 95 to 109 mm Hg, a retrospective analysis that classified subjects by the average diastolic pressure level attained during the trial purported to show an absence of treatment benefit at lower average diastolic pressures and a negative treatment effect at higher levels. However, the method of classification by average attained diastolic pressure introduced substantial selection bias, invalidating the retrospective analysis and rendering as spurious both the deleterious treatment effect and its lack of efficacy at lower diastolic levels. (<i>JAMA</i>1986;256:3134-3137)
Digestive disease: the changing scene.
Authors: H Trowell
Journal: BMJ (1973)

to an af.ernoon surgery.A general practi- tioner who holds no evening surgeries will force many patients to take time off work to visit hs doctor instead of coming to sur- gery in the evening after work.I presume Dr. Smith prefers to fall in line with the working hours of branches of the medical service working "9 to 5" rather than with his junior hospital colleagues or the majority of general practitioners.-Iam, etc.,
Application of the American Heart Association/American College of Sports Medicine Adult Preparticipation Screening Checklist to a Nationally Representative Sample of US Adults Aged ≥40 Years From the National Health and Nutrition Examination Survey 2001 to 2004
Authors: Geoffrey P. Whitfield, Kelley K. Pettee Gabriel, Mohammad H. Rahbar, Harold W. Kohl
Journal: Circulation (2014)

Although the American Heart Association/American College of Sports Medicine's Preparticipation Questionnaire (AAPQ) is a recommended preexercise cardiovascular screening tool, it has never been systematically evaluated. The purpose of this research is to provide preliminary evidence of its effectiveness among adults aged ≥40 years.
Paraoxonase-2 Reduces Oxidative Stress in Vascular Cells and Decreases Endoplasmic Reticulum Stress–Induced Caspase Activation
Authors: Sven Horke, Ines Witte, Petra Wilgenbus, Maximilian Krüger, Dennis Strand, Ulrich Förstermann
Journal: Circulation (2007)

In the vascular system, elevated levels of reactive oxygen species (ROS) produce oxidative stress and predispose to the development of atherosclerosis. Therefore, it is important to understand the systems producing and those scavenging vascular ROS. Here, we analyzed the ROS-reducing capability of paraoxonase-2 (PON2) in different vascular cells and its involvement in the endoplasmic reticulum stress pathway known as the unfolded protein response.Quantitative real-time polymerase chain reaction and Western blotting revealed that PON2 is equally expressed in vascular cells and appears in 2 distinct glycosylated isoforms. By determining intracellular ROS, we show that overexpression of PON2 markedly reduced ROS, whereas its knockdown increased ROS levels significantly. Using microscopic and biochemical methods, we found PON2 mainly in the nuclear membrane and endoplasmic reticulum. Furthermore, PON2 expression was induced at both the promoter and protein levels by endoplasmic reticulum stress pathway unfolded protein response. This pathway may promote both apoptotic and survival mechanisms. Functionally, PON2 reduced unfolded protein response-accompanying oxidative stress and unfolded protein response-derived caspase activation.We suggest that PON2 represents an endogenous defense mechanism against vascular oxidative stress and unfolded protein response-induced cell death, thereby contributing to the prevention of atherosclerosis.
Pulseless Disease (Takayasu??s Disease) Demonstrated by Radioisotope Angiography
Authors: TSUNEO HIRANO, KEIGO ENDO, AKIHIRO NAKAMURA, YASUHITO SASAKI
Journal: Clinical Nuclear Medicine (1993)

A 20-year-old woman with bilateral nonpalpable radial pulse had radioisotope angiography on the neck and thoracic inlet, which demonstrated nonvisualization of the bilateral subclavian arteries on the dynamic phase in comparison with the images on the blood pool phase. Digital subtraction angiography showed severe narrowing of the right subclavian artery and complete obstruction of the left subclavian artery.