tbuckley/cabot-search huggingface dataset:
Constrictive bronchiolitis obliterans following gold therapy for psoriatic arthritis
Authors: KJ Schwartzman, DM Bowie, C Yeadon, R Fraser, ED Sutton, RD Levy
Journal: European Respiratory Journal (1995)

A 41 year old male with psoriatic arthritis developed progressive dyspnoea and airflow obstruction following 4 months of intramuscular gold therapy. Open lung biopsy revealed bronchiolitis obliterans of the constrictive type. This case suggests a possible aetiological role for gold in the pathogenesis of constrictive bronchiolitis obliterans, or alternatively an association between psoriatic arthritis and this inflammatory airway condition.
German doctors shun eastern states
Authors: A. Tuffs
Journal: BMJ (2003)

Eastern Germany faces a dramatic shortage of doctors. In the last few years several hundred general and specialist practices in the five eastern states of Brandenburg, Mecklenburg-Western Pomerania, Thuringia, Saxony-Anhalt, and Saxony had to be closed down because vacancies could not be filled. However, with an increasing proportion of elderly people in the eastern states, medical care is in high demand.

The situation will worsen in the future, because the percentage of young doctors in Germany as a whole is decreasing: …
Prenatal risk factors of wheezing at the age of four years in Tanzania
Authors: J Sunyer
Journal: Thorax (2001)

<h3>BACKGROUND</h3> A study was undertaken to assess the interactions between prenatal exposures, early life infections, atopic predisposition, and allergen exposures in the development of wheezing up to the age of 4 years in a tropical region of Africa. <h3>METHODS</h3> The study subjects comprised children born at the district hospital in Ifakara, Tanzania during a 1 year period who were participating in a trial of iron supplementation and malaria chemoprophylaxis during the first year of life and followed for up to 4 years. From this group of subjects, 658 (79%) participated in the interview at 18 months and 528 (64%) in a second interview at 4 years. Wheezing was measured with the ISAAC questionnaire. A hospital based inpatient and outpatient surveillance system was set up to document all attendance by study children for any cause, including episodes of clinical malaria and lower respiratory tract infections. Total IgE levels and malaria parasites were measured in maternal and cord blood. Total IgE was also measured at 18 months of age. Indoor environmental levels of <i>Der p</i> I and <i>Fel d</i> I were determined using an enzyme linked immunosorbent assay at the same time as the interview at the age of 18 months. <h3>RESULTS</h3> The prevalence of wheezing at 4 years is common in Ifakara (14%, range 13–15%). The presence of malaria parasites in cord blood (odds ratio, OR = 6.84, 95% CI 1.84 to 24.0) and maternal asthma (OR = 8.47, 95% CI 2.72 to 26.2) were positively associated with wheezing at the age of 4 years, and cord blood total IgE was negatively associated (OR = 0.24, 95% CI 0.07 to 0.85) (all p&lt;0.05). Parasitaemia at birth was not related to total IgE levels in cord blood (p=0.6). Clinical episodes of malaria during infancy were not associated with wheezing, and nor were levels of indoor aeroallergens. <h3>CONCLUSION</h3> These findings suggest that events occurring during pregnancy may play a role in the future appearance of wheezing, although the results must be interpreted with caution because of the small numbers studied.
Mitochondrial Autophagy Promotes Cellular Injury in Nephropathic Cystinosis
Authors: Poonam Sansanwal, Benedict Yen, William A. Gahl, Yewei Ma, Lihua Ying, Lee-Jun C. Wong, Minnie M. Sarwal
Journal: Journal of the American Society of Nephrology (2009)

The molecular and cellular mechanisms underlying nephropathic cystinosis, which exhibits generalized proximal tubular dysfunction and progressive renal failure, remain largely unknown. Renal biopsies from patients with this disorder can reveal abnormally large mitochondria, but the relevance of this and other ultrastructural abnormalities is unclear. We studied the ultrastructure of fibroblasts and renal proximal tubular epithelial cells from patients with three clinical variants of cystinosis: Nephropathic, intermediate, and ocular. Electron microscopy revealed the presence of morphologically abnormal mitochondria and abnormal patterns of mitochondrial autophagy (mitophagy) with a high number of autophagic vacuoles and fewer mitochondria (P < 0.02) in nephropathic cystinosis. In addition, we observed increased apoptosis in renal proximal tubular epithelial cells, greater expression of LC3-II/LC3-I (microtubule-associated protein 1 light chain 3), and significantly more autophagosomes in the nephropathic variant. The autophagy inhibitor 3-methyl adenine rescued cell death in cystinotic cells. Cystinotic cells had increased levels of beclin-1 and aberrant mitochondrial function with a significant decrease in ATP generation and an increase in reactive oxygen species. This study provides ultrastructural and functional evidence of abnormal mitophagy in nephropathic cystinosis, which may contribute to the renal Fanconi syndrome and progressive renal injury.
Analysis of the Macaca mulatta transcriptome and the sequence divergence between Macaca and human.
Authors: Charles L Magness, P Campion Fellin, Matthew J Thomas, Marcus J Korth, Michael B Agy, Sean C Proll, Matthew Fitzgibbon, Christina A Scherer, Douglas G Miner, Michael G Katze, Shawn P Iadonato
Journal: Genome biology (2005)

Abstract We report the initial sequencing and comparative analysis of the Macaca mulatta transcriptome. Cloned sequences from 11 tissues, nine animals, and three species ( M. mulatta , M. fascicularis , and M. nemestrina ) were sampled, resulting in the generation of 48,642 sequence reads. These data represent an initial sampling of the putative rhesus orthologs for 6,216 human genes. Mean nucleotide diversity within M. mulatta and sequence divergence among M. fascicularis , M. nemestrina , and M. mulatta are also reported.
Caregiver Burden
Authors: Ronald D. Adelman, Lyubov L. Tmanova, Diana Delgado, Sarah Dion, Mark S. Lachs
Journal: JAMA (2014)

<h3>Importance</h3> Caregiver burden may result from providing care for patients with chronic illness. It can occur in any of the 43.5 million individuals providing support to midlife and older adults. Caregiver burden is frequently overlooked by clinicians. <h3>Objectives</h3> To outline the epidemiology of caregiver burden; to provide strategies to diagnose, assess, and intervene for caregiver burden in clinical practice; and to evaluate evidence on interventions intended to avert or mitigate caregiver burden and related caregiver distress. <h3>Evidence</h3> Cohort studies examining the relation between demographic and social risk factors and adverse outcomes of caregiver burden were reviewed. Review of recent meta-analyses to summarize the effectiveness of caregiver burden interventions were identified by searching Ovid MEDLINE, AgeLine, and the Cochrane Library. <h3>Results</h3> Risk factors for caregiver burden include female sex, low educational attainment, residence with the care recipient, higher number of hours spent caregiving, depression, social isolation, financial stress, and lack of choice in being a caregiver. Practical assessment strategies for caregiver burden exist to evaluate caregivers, their care recipients, and the care recipient's overall caregiving needs. A variety of psychosocial and pharmacological interventions have shown mild to modest efficacy in mitigating caregiver burden and associated manifestations of caregiver distress in high-quality meta-analyses. Psychosocial interventions include support groups or psychoeducational interventions for caregivers of dementia patients (effect size, 0.09-0.23). Pharmacologic interventions include use of anticholinergics or antipsychotic medications for dementia or dementia-related behaviors in the care recipient (effect size, 0.18-0.27). Many studies showed improvements in caregiver burden–associated symptoms (eg, mood, coping, self-efficacy) even when caregiver burden itself was minimally improved. <h3>Conclusions and Relevance</h3> Physicians have a responsibility to recognize caregiver burden. Caregiver assessment and intervention should be tailored to the individual circumstances and contexts in which caregiver burden occurs.
A New Rexinoid, NRX194204, Prevents Carcinogenesis in Both the Lung and Mammary Gland
Authors: Karen Liby, Darlene B. Royce, Renee Risingsong, Charlotte R. Williams, Matthew D. Wood, Roshantha A. Chandraratna, Michael B. Sporn
Journal: Clinical Cancer Research (2007)

Abstract Purpose: We evaluated the anti-inflammatory and growth-inhibitory properties of the novel rexinoid NRX194204 (4204) in vitro and then tested its ability to prevent and/or treat experimental lung and estrogen receptor (ER)–negative breast cancer in vivo. Experimental Design: In cell culture studies, we measured the ability of 4204 to block the effects of lipopolysaccharide and induce apoptosis. For the lung cancer prevention studies, A/J mice were injected with the carcinogen vinyl carbamate and then fed 4204 (30-60 mg/kg diet) for 15 weeks, beginning 1 week after the administration of the carcinogen. For breast cancer prevention studies, mouse mammary tumor virus-neu mice were fed control diet or 4204 (20 mg/kg diet) for 50 weeks; for treatment, tumors at least 32 mm3 in size were allowed to form, and then mice were fed control diet or 4204 (60 mg/kg diet) for 4 weeks. Results: Low nanomolar concentrations of 4204 blocked the ability of lipopolysaccharide and tumor necrosis factor-α to induce the release of nitric oxide and interleukin 6 and the degradation of IKBα in RAW264.7 macrophage-like cells. In the A/J mouse model of lung cancer, 4204 significantly (P &amp;lt; 0.05) reduced the number and size of tumors on the surface of the lungs and reduced the total tumor volume per slide by 64% to 81% compared with the control group. In mouse mammary tumor virus-neu mice, 4204 not only delayed the development of ER-negative mammary tumors in the prevention studies but also caused marked tumor regression (92%) or growth arrest (8%) in all of the mammary tumors when used therapeutically. Conclusions: The combined anti-inflammatory and anticarcinogenic actions of 4204 suggest that it is a promising new rexinoid that should be considered for future clinical trials.
What's Happening to Clinical Teaching?
Authors: J. Fred Mullins
Journal: JAMA (1968)

Clinical teaching is passé. On what do I base that statement? Nineteen years of sincere and interested involvement in medical student teaching. Most deans and medical school officials have spent their time acquiring federal grants and building research institutes and physical structures to the neglect of developing and supporting teachers in medicine. When a new department chairman is to be appointed, the search committee almost never inquires as to the individual's teaching capabilities or his interest in this dimension. The officials are concerned with how much grant money he can bring with him, how has he done with governmental grantsmanship, and what are his possibilities for the future along these lines. Ask any young faculty member as to what criteria are used in his institution for promotions and they will all say the "weight" and number of research papers, not necessarily the quality. This promotion rarely is based on whether or not he has done a good job teaching or carries a heavy clinical service load. Their future depends on research production and, when their time is at a premium, the
Truncations of Titin Causing Dilated Cardiomyopathy
Authors: Daniel S. Herman, Lien Lam, Matthew R.G. Taylor, Libin Wang, Polakit Teekakirikul, Danos Christodoulou, Lauren Conner, Steven R. DePalma, Barbara McDonough, Elizabeth Sparks, Debbie Lin Teodorescu, Allison L. Cirino, Nicholas R. Banner, Dudley J. Pennell, Sharon Graw, Marco Merlo, Andrea Di Lenarda, Gianfranco Sinagra, J. Martijn Bos, Michael J. Ackerman, Richard N. Mitchell, Charles E. Murry, Neal K. Lakdawala, Carolyn Y. Ho, Paul J.R. Barton, Stuart A. Cook, Luisa Mestroni, J.G. Seidman, Christine E. Seidman
Journal: New England Journal of Medicine (2012)

Dilated cardiomyopathy and hypertrophic cardiomyopathy arise from mutations in many genes. TTN, the gene encoding the sarcomere protein titin, has been insufficiently analyzed for cardiomyopathy mutations because of its enormous size.
Capecitabine combined with oxaliplatin (CapOx) in clinical practice: how significant is peripheral neuropathy?
Authors: D.J. Storey, M. Sakala, C.M. McLean, H.A. Phillips, L.K. Dawson, L.R. Wall, M.T. Fallon, S. Clive
Journal: Annals of Oncology (2010)
Evolution of Spontaneous Atherosclerotic Plaque Rupture With Medical Therapy
Authors: Gilles Rioufol, Martine Gilard, Gérard Finet, Isabelle Ginon, Jacques Boschat, Xavier André-Fouët
Journal: Circulation (2004)

Ruptured coronary atheromatous plaque is generally considered to involve a high risk of subsequent clinical events. Few data are available on the natural evolution of non-culprit-lesion ruptured plaque. We therefore used serial intravascular ultrasound (IVUS) to study how such lesions, detected in the context of a first acute coronary syndrome with elevated troponin I levels, develop.Fourteen patients with 28 distinct plaque ruptures (2+/-1 per patient) without significant associated stenosis (minimal lumen cross-sectional area >4 mm2) were included and systematically treated with 40 mg statin and antiplatelet agent (clopidogrel and aspirin for > or =9 months). Mean clinical and IVUS follow-up was 22+/-13 months (median, 22 months). No clinical event related to the lesion under study occurred. On final IVUS examination, half (14 of 28) of the ruptured plaques had healed, and the degree of stenosis tended to diminish (stenosis, 22+/-17% versus 29+/-17% at baseline; P=0.056). No healing-prediction criterion could be identified.Nearly 2 years of follow-up found that spontaneous coronary atheromatous plaque rupture without significant stenosis detected on first acute coronary syndrome healed without significant plaque modification in 50% of cases with medical therapy.
Detection of Liver Metastases From Endocrine Tumors: A Prospective Comparison of Somatostatin Receptor Scintigraphy, Computed Tomography, and Magnetic Resonance Imaging
Authors: Clarisse Dromain, Thierry de Baere, Jean Lumbroso, Hubert Caillet, Agnès Laplanche, Valerie Boige, Michel Ducreux, Pierre Duvillard, Dominique Elias, Martin Schlumberger, Robert Sigal, Eric Baudin
Journal: Journal of Clinical Oncology (2004)

To compare the respective sensitivity of somatostatin receptor scintigraphy (SRS), computed tomography (CT), and magnetic resonance imaging (MRI) in the detection of liver metastases from well-differentiated gastroenteropancreatic endocrine tumor (WDGEP ET) patients. To define predictive factors for "high-sensitivity SRS."Sixty-four patients with WDGEP ET underwent SRS with abdominal single-photon emission computed tomography (SPECT), spiral CT, and 1.5-T MRI within a 15-day interval, the order of which was randomized. Two readers analyzed images of each modality, blindly and independently.Hepatic metastases were present in 40 of the 64 patients and confirmed by pathology after liver biopsy or surgery in 32 and eight patients, respectively. SRS, CT, and MRI detected a total of 204, 325, and 394 metastases, respectively. The number of detected metastases was significantly higher with MRI than with CT (P = .02) and SRS (P < 10(-4)) and higher with CT than with SRS (P < 10(-4)). SRS was negative in seven patients with a positive CT and/or MRI. More lesions were detected in 10 patients by SPECT compared with static views. The median metastasis size was significantly correlated (P = .04) with the sensitivity of SRS.MRI seems to have an edge over CT and SRS for the detection of liver metastases from endocrine tumors. We recommend the systematic performance of liver MRI at WDGEP ET initial staging and before major therapeutic events. The low performance of SRS was mainly explained by the impact of the metastasis size on the detection capacity of SRS.
Extrathoracic proof of intrathoracic trouble
Authors: C Dickhoff, K J Hartemink, D J Slebos, P Symersky, A Vonk-Noordegraaf
Journal: Thorax (2013)

A 67-year-old man was referred to our hospital for bullectomy. Chest CT scan showed exhaustive bilateral bullous emphysema with a giant bulla in the right lung (figure 1). Cardiopulmonary exercise testing revealed a maximum exercise tolerance of 30 Watts and a progressive dynamic hyperinflation with an inspiratory capacity …
Glucocorticoids inhibit degranulation of mast cells in allergic asthma via nongenomic mechanism
Authors: J. Zhou, D.‐F. Liu, C. Liu, Z.‐M. Kang, X.‐H. Shen, Y.‐Z. Chen, T. Xu, C.‐L. Jiang
Journal: Allergy (2008)

Background: Glucocorticoids (GCs) are the most potent anti‐inflammatory agents available for allergic diseases including asthma, which are routinely believed to need several hours to take effect through regulating gene expression. Our previous report had shown that GCs could inhibit allergic asthma within 10 min, which the classical mechanism could not explain. Objective: To confirm the existence and verify the sites of GCs’ rapid action, we investigated nongenomic effects of GCs on degranulation of mast cells in allergic asthma. Methods: The GCs’ rapid action on airway mast cells deregulations was evaluated in the allergic asthma model of guinea pigs by the computer‐assisted morphometry. Using whole‐cell patch clamp and fluorometric assay, we examined GCs’ nongenomic effect on IgE‐mediated exocytosis and histamine release of rat basophilic leukaemia‐2H3 mast cells. Employing the flash photolysis technique, we studied the role of Ca 2+ signal in the GCs’ nongenomic effect. Results: Inhaled GCs significantly inhibited airway mast cells degranulation in the allergic asthma model of guinea pigs within 10 min. In vitro , GCs could rapidly inhibit IgE‐mediated exocytosis and histamine release of mast cells, and neither GC nuclear receptor antagonist nor protein synthesis inhibitor could block the rapid action. We further demonstrated that GCs’ nongenomic effect was not through direct action on secretory machinery, but was mediated by a reduction in the [Ca 2+ ] i elevation. Conclusions: The study suggested for the first time that nongenomic pathway was involved in GCs’ rapid inhibition on allergic asthma, and raised the possibility of new therapeutic strategies for allergic diseases including asthma.
Effect of Serum 25-Hydroxyvitamin D on Risk for Type 2 Diabetes May Be Partially Mediated by Subclinical Inflammation
Authors: Barbara Thorand, Astrid Zierer, Cornelia Huth, Jakob Linseisen, Christa Meisinger, Michael Roden, Annette Peters, Wolfgang Koenig, Christian Herder
Journal: Diabetes Care (2011)

To assess the association between serum 25-hydroxyvitamin D (25-OHD) and incident type 2 diabetes and to determine whether the association is mediated by subclinical inflammation.Using a case-cohort design, baseline levels of 25-OHD were measured in 416 case subjects with incident type 2 diabetes and 1,267 noncase subjects selected from a source population of 7,936 middle-aged participants in the population-based Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) study.A significant inverse association was observed between serum 25-OHD and incident type 2 diabetes after adjustment for diabetes risk factors and season. The hazard ratio (HR) and 95% CI comparing tertile extremes was 0.63 (0.44-0.90) (P(trend) = 0.010). Further adjustment for C-reactive protein, interleukin-6, soluble intercellular adhesion molecule-1, and interferon-γ-inducible protein-10 attenuated this association by 16% (HR 0.73 [0.50-1.05], P = 0.090).Vitamin D status is inversely related to type 2 diabetes risk and our data suggest that this association may be partially mediated by subclinical inflammation.
Secondary localized cutaneous amyloidosis in solar elastosis
Authors: T. TSUJI, Y. ASAI, T. HAMADA
Journal: British Journal of Dermatology (1982)

A case of secondary localized cutaneous amyloidosis in solar elastosis was studies by light and electron microscopy. Amyloid deposition was restricted to areas with elastotic changes, and in some areas both changes were intermingled with each other. The amyloid was permanganate-sensitive, and proved to be protein AA. Ultrastructurally it was composed of fine tubular filaments. It is suggested that the amyloid deposition in this case was related to sunlight damage of the skin.
Biochemical Identification of a Mutated Human Melanoma Antigen Recognized by CD4+ T Cells
Authors: Rembert Pieper, Robert E. Christian, Monica I. Gonzales, Michael I. Nishimura, Gaorav Gupta, Robert E. Settlage, Jeffrey Shabanowitz, Steven A. Rosenberg, Donald F. Hunt, Suzanne L. Topalian
Journal: The Journal of Experimental Medicine (1999)

CD4+ T cells play a critical role in generating and maintaining immune responses against pathogens and alloantigens, and evidence suggests an important role for them in antitumor immunity as well. Although major histocompatibility complex class II–restricted human CD4+ T cells with specific antitumor reactivities have been described, no standard method exists for cloning the recognized tumor-associated antigen (Ag). In this study, biochemical protein purification methods were used in conjunction with novel mass spectrometry sequencing techniques and molecular cloning to isolate a unique melanoma Ag recognized by a CD4+ tumor-infiltrating lymphocyte (TIL) line. The HLA-DRβ1*0101–restricted Ag was determined to be a mutated glycolytic enzyme, triosephosphate isomerase (TPI). A C to T mutation identified by cDNA sequencing caused a Thr to Ile conversion in TPI, which could be detected in a tryptic digest of tumor-derived TPI by mass spectrometry. The Thr to Ile conversion created a neoepitope whose T cell stimulatory activity was enhanced at least 5 logs compared with the wild-type peptide. Analysis of T cell recognition of serially truncated peptides suggested that the mutated amino acid residue was a T cell receptor contact. Defining human tumor Ag recognized by T helper cells may provide important clues to designing more effective immunotherapies for cancer.
Lack of correlation between numbers of circulating t(14;18)-positive cells and response to first-line treatment in follicular lymphoma
Authors: Caroline M. P. W. Mandigers, Jules P. P. Meijerink, Ewald J. B. M. Mensink, Evelyn L. R. T. M. Tönnissen, Konnie M. Hebeda, M. José J. T. Bogman, John M. M. Raemaekers
Journal: Blood (2001)
The Application of the Galvanic Cautery to Gynaecology
Authors: J. B. Hicks
Journal: BMJ (1874)

MEDICAL 70URNAL.[Nov. 28, I874, it is very much better that the law should be distinict and certain, and that this quasi-legislative authority should not be left in the hands of the judges."The law of murder, then, is declared to be such that the judges con- tradict each other; and yet they make it themselves, and maintain it in its present discreditable state, because it enables them to occupy a position, as its authoritative exponents, which is agreeable to them, and from which they do niot like to be ousted.I thinlk you will conclude that Mr. Fitzjames Stephen is not only learned and skilful, as the Committee declare him to be, but very outspoken.With regar-d to our great judges, I hope you will also think that he has been a little hard- spoken and too severe.