tbuckley/cabot-search huggingface dataset:
Cigarette smoking and rheumatoid arthritis severity
Authors: K. G Saag, J. R Cerhan, S. Kolluri, K. Ohashi, G. W Hunninghake, D. A Schwartz
Journal: Annals of the Rheumatic Diseases (1997)

Cigarette smoking may influence rheumatoid arthritis (RA) disease incidence and may have direct biological effects on the lungs and systemically. This study sought to determine if cigarette smoking is associated with RA disease severity.Clinical evaluations of patients seen in the University of Iowa rheumatology and orthopaedic ambulatory clinics were conducted. A letter of interest was mailed to 1701 patients who were first assigned an ICD-9-CM diagnostic code for RA in one of these clinics. A total of 857 patients expressed interest and were offered a clinical examination and 395 were evaluated over an 18 month period. Of these, 336 satisfied examiner criteria for prevalent RA and were included in the analysis. The disease characteristics and arthritis care utilisation of these patients seemed representative of prevalent cases in the general community. RA disease severity was assessed by radiographic bone erosions (graded as either present/ absent and using the Larsen system), rheumatoid factor seropositivity, and presence of subcutaneous rheumatoid nodules.Pack years of cigarette smoking was significantly associated with rheumatoid factor seropositivity (p = 0.0001), radiographic erosions (p = 0.024), and nodules (p = 0.051). After adjustment for potential confounders, smokers with > or = 25 pack years were 3.1 times more likely to be rheumatoid factor positive (95% CI 1.7, 5.6) and 2.4 times more likely to show radiographic erosions (95% CI 1.2, 4.5) than never smokers. Less severe radiographic disease seemed to be more strongly associated with cigarette smoking than more severe disease.Cigarette smoking may adversely influence the severity of RA in a potentially dose dependent fashion.
Cardiac remodelling during pregnancy: whither the guinea pig?
Authors: Michael J. Taggart, Richard Hume, Jon Lartey, Mark Johnson, Wing-Chiu Tong, Kenneth T. Macleod
Journal: Cardiovascular Research (2014)

This letter refers to ‘Pregnancy as a cardiac stress model’ by E. Chung and L.A. Leinwand, Cardiovascular Research 2014;101:561–570 

We were interested to read the recent article published by Chung and Leiwand1 entitled Pregnancy as a Cardiac Stress Model . This, and allied articles in the Review Focus on Pregnancy-mediated Heart and Vascular Disease, eloquently brought attention to an important, yet much understudied, theme. Namely, that there is much to be learnt from elucidating the remodelling responses to the cardiovascular challenge of pregnancy that may be beneficial to informing our understanding of the sequence of events leading to compensating cardiac hypertrophy and the deleterious changes beyond those which initiate and underpin progression to heart failure.

Much of the experimental data reviewed by Chung and Leiwand1 was derived from mouse or rat models. This is understandable for reasons of cost, accessibility, and ease of genetic manipulation that facilitate mechanistic experimentation in a timely fashion. An additional important feature of the Chung and Leiwand1 article was to draw distinctions between exercise-induced remodelling and pregnancy-dependent adaptations, and the majority of work in the former category has also been undertaken in rat or mouse models. This therefore offers a basis on which to compare the two physiological remodelling circumstances.

Notwithstanding these benefits, one should also recognize where limits reside for extrapolating information from mouse or rat models of cardiac function in pregnancy to the human. There …
Multivariate analysis of factors associated with early-onset segmental and nonsegmental vitiligo: a prospective observational study of 213 patients
Authors: K. Ezzedine, A. Diallo, C. Léauté-Labrèze, D. Mossalayi, Y. Gauthier, S. Bouchtnei, M. Cario-André, J. Seneschal, F. Boralevi, T. Jouary, A. Taieb
Journal: British Journal of Dermatology (2011)

Although mixed forms have been described recently, segmental (SV) and nonsegmental vitiligo (NSV) are considered as clinically distinct. However, limited epidemiological data are available to help distinguish associated factors, and recent genome-wide association studies have been restricted to NSV. The higher prevalence of SV in children is helpful when comparing the two major presentations of the disease.To compare factors associated with SV and NSV, especially for markers of autoimmunity or autoinflammation.We conducted a single-centre prospective observational study in patients aged 17 years or under with a confirmed diagnosis of SV or NSV at the vitiligo clinic between 1 January 2006 and 1 July 2010. The Vitiligo European Task Force questionnaire was completed for each patient, and thyroid function and antithyroid antibodies were screened if not obtained in the previous year. Other forms of vitiligo (focal, mucosal, not classifiable) were excluded.A total of 213 children were included, 142 with NSV, 59 with SV and 12 with mixed vitiligo. There was no significant statistical difference for sex or age at onset between patients with SV and NSV. Halo naevi were significantly more frequent in NSV than in SV [odds ratio (OR) 7·58, P < 0·01). Patients with NSV more frequently had a positive family history of vitiligo (OR 2·25, P=0·02) and a marked familial autoimmunity background (OR 2·22, P = 0·01).Our study clearly shows that features of inflammation (pruritus)/autoimmunity (halo naevi, thyroid antibodies) are strongly linked to NSV, together with a familial background of vitiligo and autoimmunity.
The Mechanics of Esophageal Muscle Contraction. EVIDENCE OF AN INOTROPIC EFFECT OF GASTRIN
Authors: Sidney Cohen, Fe Green
Journal: Journal of Clinical Investigation (1973)

To compare the mechanical properties of lower esophageal sphincter (LES) and esophageal circular smooth muscle, force-velocity determinations were made under various physiological conditions. Isotonic and isometric recordings of opossum circular muscle were used to obtain the velocity of shortening and force, respectively, during alterations in: (a) initial muscle length (preload), (b) afterload, (c) calcium concentration, and (d) gastrin I. Muscle contraction was elicited to the neurogenic response at the termination of electrical stimulation. A change in preload (muscle length) altered the peak force (Po) developed during an afterloaded contraction, but had only a minor effect on the maximum velocity of shortening (V max). At the length of optimal tension development, Lo, (preload, 1.5 g), the LES muscle had a V max of 6.1+/-0.2 mm/s and a Po of 17.7+/-0.7 g. The esophageal muscle at its Lo (preload, 2.0 g) had a V max of 6.3+/-0.5 mm/s and a Po of 18.1+/-1.2 g. A decrease in calcium from 2.5 mM to 1.0 mM significantly reduced the V max and Po of all muscle, but an increase in calcium to 5.0 mM increased these parameters only minimally. At a calcium of 1.0 mM, gastrin I increased both V max and Po of all muscle. This inotropic effect of gastrin I occurred at lower concentrations in LES muscle than in muscle from the upper esophagus. The power (force x velocity) and work (force x muscle shortening) of esophageal and LES muscle were calculated from these data. Both the work and power generated during esophageal and LES muscle contraction were determined by: (a) the initial muscle length as produced by the preload, (b) the afterload against which the muscle was contracting, and (c) the contractility of inotropism of the muscle, that is, the force-velocity curve on which the muscle was operating.
Clinical features and diagnosis of aspirin induced asthma
Authors: A. Szczeklik
Journal: Thorax (2000)

Although for therapeutic reasons it has become convenient to consider asthma as a single disease entity, this clearly is not the case, with many variants occurring.From a clinical standpoint, a minimal subdivision includes atopic asthma, cough variant asthma, brittle asthma, intrinsic asthma, occupational non-IgE dependent asthma, and aspirin intolerant asthma (AIA). 1 This last variant constitutes a clearcut clinical syndrome.It is a remarkable model for investigating mechanisms that operate in asthma, rhinitis, and nasal polyposis.The recent introduction of anti-leukotriene drugs has amplified interest in this syndrome. Definition, prevalence and clinical presentationAIA is an aggressive mucosal inflammatory disease combined with precipitation of asthma and rhinitis attacks which occurs after ingestion of aspirin and most non-steroidal antiinflammatory drugs (NSAID). 2 Aspirin intolerance is underdiagnosed within the asthmatic population.Based on patients' history alone, the incidence of aspirin sensitivity in adult asthmatics is 3-5%, but this rises to 19% of consecutive adult asthmatic patients challenged with oral aspirin.Even in adult asthmatics with no history of aspirin intolerance, 9% show sensitivity to oral aspirin challenge and in those with rhinosinusitis the figure rises to 34%. 3 The reasons for underreporting of aspirin sensitivity may include the deliberate avoidance of NSAIDs by asthmatic patients who are aware of adverse reactions, or a lack of recognition by patients of mild NSAID induced reactions because of their delayed onset of action.Thus, in a population of 500 patients with AIA studied in the European Network of Aspirin-Induced Asthma (AIANE), 18% were unaware of aspirin intolerance before having aspirin provocation tests.This indicates that underdiagnosis of aspirin sensitivity may be due to the lack of routine aspirin challenge testing of asthmatic patients who do not report a positive history of aspirin sensitivity.In most patients (women are aVected 2.5 times more often than men), symptoms of rhinitis first occur during the third decade, often after a viral respiratory illness. 2 4 5 Over a period of months, chronic nasal congestion, anosmia, and rhinorrhoea develop.Physical examination often reveals nasal polyps.Bronchial asthma and sensitivity to aspirin develops next.After ingestion of aspirin or an NSAID, an acute asthma attack occurs within a few minutes up to three hours, usually accompanied by profuse rhinorrhoea, conjunctival
Natural Selection in Gene-Dense Regions Shapes the Genomic Pattern of Polymorphism in Wild and Domesticated Rice
Authors: J. M. Flowers, J. Molina, S. Rubinstein, P. Huang, B. A. Schaal, M. D. Purugganan
Journal: Molecular Biology and Evolution (2011)

Levels of nucleotide variability are frequently positively correlated with recombination rate and negatively associated with gene density due to the effects of selection on linked variation. These relationships are determined by properties that frequently differ among species, including the mating system, and aspects of genome organization such as how genes are distributed along chromosomes. In rice, genes are found at highest density in regions with frequent crossing-over. This association between gene density and recombination rate provides an opportunity to evaluate the effects of selection in a genomic context that differs from other model organisms. Using single-nucleotide polymorphism data from Asian domesticated rice Oryza sativa ssp. japonica and ssp. indica and their progenitor species O. rufipogon, we observe a significant negative association between levels of polymorphism and both gene and coding site density, but either no association, or a negative correlation, between nucleotide variability and recombination rate. We establish that these patterns are unlikely to be explained by neutral mutation rate biases and demonstrate that a model of background selection with variable rates of deleterious mutation is sufficient to account for the gene density effect in O. rufipogon. In O. sativa ssp. japonica, we report a strong negative correlation between polymorphism and recombination rate and greater losses of variation during domestication in the euchromatic chromosome arms than heterochromatin. This is consistent with Hill–Robertson interference in low-recombination regions, which may limit the efficacy of selection for domestication traits. Our results suggest that the physical distribution of selected mutations is a primary factor that determines the genomic pattern of polymorphism in wild and domesticated rice species.
A Case of Adiposis Dolorosa
Authors: W. H. White
Journal: BMJ (1899)

sharp, burning, or scalding, and is frequently paroxysmal, A CASE OF ADIPOSIS DOLOROSA.but then there is usually slight pain between the paroxysms.( With 111ustration8.)The patient often complains early in the course of the disease ByW.HALEWiHITEtrtMn.)., F.R.C.P., of a sense of coldness, and if examined when the disease is
Big and Little Forms of Osteoclast Activating Factor
Authors: Gregory R. Mundy, Lawrence G. Raisz, James L. Shapiro, Janet G. Bandelin, Robert J. Turcotte
Journal: Journal of Clinical Investigation (1977)

We have further characterized osteoclast activating factor (OAF) using a bioassay for bone resorption which utilizes the release of previously incorporated 45Ca from fetal rat long bones in organ culture. When supernatant media from activated leukocyte cultures were concentrated on Amicon PM10 membranes (assigned molecular weight cutoff 10,000 daltons) and chromatographed on Sephadex G-50 columns, the bone-resorbing activity eluted between the molecular weight markers chymotrypsinogen (25,000 daltons) and cytochrome c (12,500 daltons). This peak of biological activity has been called big OAF. When filtrates from the PM10 membranes were concentrated on Amicon UM2 membranes (assigned molecular weight cutoff 1,000 daltons) and chromatographed on Sephadex G-50 columns, some of the biological activity eluted between the molecular weight markers chymotrypsinogen and cytochrome c (big OAF), but there was a separate peak of biological activity which eluted with [3H]proline (140 daltons). This second peak has been called little OAF. Little OAF was eluted from Bio-Gel P6 columns between the molecular weight markers calcitonin (approximately 3,500 daltons) and vitamin B12 (1,330 daltons), but was retained by Spectrapor dialysis tubing (nominal molecular weight cutoff 3,500 daltons). Big OAF was converted to little OAF by equilibration in 1 M NaCl or 2 M urea. Little OAF was self-associated back to big OAF by equilibration in buffers of low ionic strength (Tris-HCl 10-50 mM). Little OAF was extracted into the organic phase in ethyl acetate after acidification of the sample to pH 3.5. The biological activity remained in the aqueous phase after ethyl acetate extraction at pH 7.5-8.4. Little OAF has been purified more than 6,000-fold compared with the original material so that bone-resorbing activity is maximal in a sample with a protein concentration of 80 ng/ml.
Differential Platelet Levels Affect Response to Taxane-Based Therapy in Ovarian Cancer
Authors: Justin Bottsford-Miller, Hyun-Jin Choi, Heather J. Dalton, Rebecca L. Stone, Min Soon Cho, Monika Haemmerle, Alpa M. Nick, Sunila Pradeep, Behrouz Zand, Rebecca A. Previs, Chad V. Pecot, Erin King Crane, Wei Hu, Susan K. Lutgendorf, Vahid Afshar-Kharghan, Anil K. Sood
Journal: Clinical Cancer Research (2014)

We hypothesized that platelet levels during therapy could serve as a biomarker for response to therapy and that manipulation of platelet levels could impact responsiveness to chemotherapy.The medical records of patients with recurrent or progressive ovarian cancer were retrospectively queried for changes in platelet and CA-125 levels during primary therapy. In vitro coculture experiments and in vivo orthotopic models of human ovarian cancer in mice were used to test the effect of modulating platelet levels on tumor growth and responsiveness to docetaxel.Thrombocytosis at the diagnosis of ovarian cancer was correlated with decreased interval to progression (P = 0.05) and median overall survival (P = 0.007). Mean platelet levels corrected during primary therapy and rose at recurrence. Contrary to treatment-responsive patients, in a cohort of patients refractory to primary therapy, platelet levels did not normalize during therapy. In A2780, HeyA8, and SKOV3-ip1 ovarian cancer cell lines, platelet coculture protected against apoptosis (P < 0.05). In orthotopic models of human ovarian cancer, platelet depletion resulted in 70% reduced mean tumor weight (P < 0.05). Compared with mice treated with docetaxel, mice treated with both docetaxel and platelet-depleting antibody had a 62% decrease in mean tumor weight (P = 0.04). Platelet transfusion increased mean aggregate tumor weight 2.4-fold (P < 0.05), blocked the effect of docetaxel on tumor growth (P = 0.55) and decreased tumor cell apoptosis. Pretransfusion aspirinization of the platelets blocked the growth-promoting effects of transfusion.Platelet-driven effects of chemotherapy response may explain clinical observations.
Guidelines on the management of osteoporosis associated with chronic liver disease
Authors: J D Collier
Journal: Gut (2002)

An important complication of chronic liver disease is osteodystrophy which includes osteoporosis and the much rarer osteomalacia. Both conditions are associated with significant morbidity through fractures resulting in pain, deformity, and immobility. There is also a further significant increase in the risk of fractures following liver transplantation for end stage chronic liver disease.

Osteoporosis is defined as a “progressive systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture” (World Health Organisation, 1994). Common fractures are vertebral compression fractures, fractures of the distal radius, and proximal femur.

Although guidelines on the prevention and management of osteoporosis, and specifically corticosteroid induced osteoporosis and osteoporosis in men, have recently been published, there is no consensus on how to manage osteoporosis in patients with chronic liver disease.1–3

The scope of these guidelines is to review the assessment and diagnosis of osteoporosis, the therapeutic agents available, and the way in which they can be used in patients with chronic liver disease to prevent osteoporosis with the aim of reducing fracture rate. A number of research priorities have also been identified.

### 2.1 Grading of recommendations and evidence level in patients with chronic liver disease

The guidelines developed are based on systematic review of the published literature. As not all recommendations are based on randomised controlled trials, the recommendations have been scored according to the following criteria.

Grade A: based on meta-analysis or at least one randomised controlled trial.

Grade B: based on at least one well designed but not necessarily controlled study including case control and comparative studies.

Grade C: based on expert reports or opinions.

### 2.2 Process of guideline formation

A systematic review of the literature was undertaken and draft guidelines prepared. The guidelines were then reviewed in a consensus workshop following which a final draft was prepared. The consensus workshop was supported by the …
Risk of Bilateral Testicular Germ Cell Cancer in Denmark: 1960-1984
Authors: A. Osterlind, J. G. Berthelsen, N. Abildgaard, S. O. Hansen, H. Hjalgrim, B. Johansen, J. Munck-Hansen, L. H. Rasmussen
Journal: JNCI Journal of the National Cancer Institute (1991)

The incidence of a second primary testicular germ cell cancer among 2850 (96.6% of eligible) men with a histologically verified first primary germ cell cancer diagnosed in the period 1960–1979 in Denmark was established. Of these 2850 men, 73 (2.6%) developed a contralateral testicular cancer. In five of these patients (0.18%), the tumors were synchronous. The cumulative risk of developing a contralateral cancer 25 years after diagnosis of the first testicular germ cell cancer was 5.2% according to a Kaplan–Meier estimate. It was higher among men with a nonseminoma as the first tumor (8.4%) than among men with a seminoma as the first tumor (3.6%). Of the second tumors, 12% were stage II and 17% were stage III at the time of diagnosis. Based on 24 588 person–years at risk and 68 nonsimultaneously occurring bilateral testicular germ cell cancers, the overall relative risk (RR) of developing a second primary cancer in the contralateral tes ticle following a first germ cell cancer was found to be 24.8 (95% confidence interval = 19–38). Among men with a nonseminoma, the risk was higher (RR = 27.1) than among men with a seminoma (RR = 22.5). The excess risk was not affected by age at diagnosis, calendar period, or time since diagnosis. Close surveillance by screening for and treatment of carcinoma in situ of the remaining testicle in testicular cancer patients are advised. [J Natl Cancer Inst 83:1391–1395, 1991]
Benchmarking antimicrobial drug use at university hospitals in five European countries
Authors: V. Vlahović-Palčevski, U. Dumpis, P. Mitt, J. Gulbinovič, J. Struwe, G. Palčevski, D. Štimac, Å. Lagergren, U. Bergman
Journal: Clinical Microbiology and Infection (2006)
SULFATE-SULFUR METABOLISM IN THE RAT FETUS AS INDICATED BY SULFUR-35
Authors: Dominic D. Dziewiatkowski
Journal: The Journal of Experimental Medicine (1953)

Twenty-four hours after the intraperitoneal injection of sodium sulfate-S35 into pregnant rats, sulfur-35 was found in the embryos. The amount of the sulfur-35 retained by the embryos was directly related to their degree of development in utero. A large fraction of the sulfur-35 found in the embryos was insoluble in 5 per cent trichloroacetic acid. At the 9th to 10th day of development, about 40 per cent of the sulfur-35 was present in this fraction. In 20-day-old embryos this fraction accounted for nearly 90 per cent of the total. Radioautographs of sections of embryos fixed in a solution of formaldehyde revealed that the sulfur-35 was most highly concentrated in the cartilaginous portion of the skeleton. All other tissues gave much weaker autographic reactions, comparable with the over-all reaction obtained when sections from embryos fixed in a solution of formaldehyde saturated with barium hydroxide were used. By analysis for the sulfur-35 content of individual tissues the concentration of the sulfur-35 in humeri from 20-day-old embryos was found to be about 30 times that in the maternal sternum. The concentration of the isotope in the skeletal muscle, brain, heart, and skin of the same embryos was also higher than in the corresponding maternal tissues. On the other hand, the concentration of the sulfur-35 in the maternal gastrointestinal tract plus contents was higher than in the gastrointestinal tract and contents of the embryos.