tbuckley/cabot-search huggingface dataset:
Randomized, Open-Label, Phase III Study Comparing Irinotecan With Paclitaxel in Patients With Advanced Gastric Cancer Without Severe Peritoneal Metastasis After Failure of Prior Combination Chemotherapy Using Fluoropyrimidine Plus Platinum: WJOG 4007 Trial
Authors: Shuichi Hironaka, Shinya Ueda, Hirofumi Yasui, Tomohiro Nishina, Masahiro Tsuda, Takehiko Tsumura, Naotoshi Sugimoto, Hideki Shimodaira, Shinya Tokunaga, Toshikazu Moriwaki, Taito Esaki, Michitaka Nagase, Kazumasa Fujitani, Kensei Yamaguchi, Takashi Ura, Yasuo Hamamoto, Satoshi Morita, Isamu Okamoto, Narikazu Boku, Ichinosuke Hyodo
Journal: Journal of Clinical Oncology (2013)

This phase III study compared treatment with weekly paclitaxel and biweekly irinotecan in patients with advanced gastric cancer refractory to treatment with fluoropyrimidine plus platinum.Patients were randomly assigned to receive either paclitaxel (80 mg/m(2) on days 1, 8, and 15, every 4 weeks) or irinotecan (150 mg/m(2) on days 1 and 15, every 4 weeks). Primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), response rate, adverse events, and proportion of patients who received third-line chemotherapy.Of 223 patients, 219 were eligible for analysis. Median OS was 9.5 months in 108 patients allocated to the paclitaxel group and 8.4 months in 111 patients allocated to the irinotecan group (hazard ratio [HR], 1.13; 95% CI, 0.86 to 1.49; P = .38). Median PFS was 3.6 months in the paclitaxel group and 2.3 months in the irinotecan group (HR, 1.14; 95% CI, 0.88 to 1.49; P = .33). Response rate was 20.9% in the paclitaxel group and 13.6% in the irinotecan group (P = .24). Common grade 3 to 4 adverse events were neutropenia (paclitaxel group, 28.7%; irinotecan group, 39.1%), anemia (21.3%; 30.0%), and anorexia (7.4%; 17.3%). Treatment-related deaths occurred in two patients (1.8%) in the irinotecan group. Third-line chemotherapy was administered in 97 patients (89.8%) after paclitaxel treatment and in 80 patients (72.1%) after irinotecan treatment (P = .001).No statistically significant difference was observed between paclitaxel and irinotecan for OS. Both are reasonable second-line treatment options for advanced gastric cancer.
Multispectral scanning during endoscopy guides biopsy of dysplasia in Barrett's esophagus
Authors: Le Qiu, Douglas K Pleskow, Ram Chuttani, Edward Vitkin, Jan Leyden, Nuri Ozden, Sara Itani, Lianyu Guo, Alana Sacks, Jeffrey D Goldsmith, Mark D Modell, Eugene B Hanlon, Irving Itzkan, Lev T Perelman
Journal: Nature Medicine (2010)
Bone turnover during high dose inhaled corticosteroid treatment.
Authors: N J Ali, S Capewell, M J Ward
Journal: Thorax (1991)

This study was performed to determine the effects of high doses of two inhaled corticosteroids, beclomethasone dipropionate and budesonide, on biochemical indices of bone turnover (urinary hydroxyproline:creatine and calcium:creatinine ratios, plasma alkaline phosphatase, and parathyroid hormone). Twelve healthy male doctors, aged 25-36 (mean 30) years, were studied. After a week's run in period eight subjects inhaled beclomethasone dipropionate 2000 micrograms/day and eight inhaled budesonide 1800 micrograms/day for 28 days; this was followed by a week without any treatment. During treatment with beclomethasone dipropionate there was a significant increase in the hydroxyproline:creatinine ratio (a 46% increase at 28 days), and a fall in serum alkaline phosphatase activity (a 7.4% fall at 28 days). There were no significant changes during budesonide treatment. Thus high dose inhaled beclomethasone dipropionate increased biochemical markers of bone resorption and reduced serum alkaline phosphatase, a marker of bone mineralisation. A prospective study in asthmatic patients is indicated to assess the long term effects of high dose inhaled corticosteroids on bone mass.
Inferring genome-scale rearrangement phylogeny and ancestral gene order: a Drosophila case study
Authors: Arjun Bhutkar, William M Gelbart, Temple F Smith
Journal: Genome biology (2007)

A simple, fast, and biologically inspired computational approach for inferring genome-scale rearrangement phylogeny and ancestral gene order has been developed. This has been applied to eight Drosophila genomes. Existing techniques are either limited to a few hundred markers or a small number of taxa. This analysis uses over 14,000 genomic loci and employs discrete elements consisting of pairs of homologous genetic elements. The results provide insight into evolutionary chromosomal dynamics and synteny analysis, and inform speciation studies.
Evaluation of effectiveness of good growth monitoring in south Indian villages
Authors: S.M. George, M.C. Latham, E.A. Frongillo, R. Abel, N. Ethirajan
Journal: The Lancet (1993)

We conducted a community intervention trial in 12 villages in Tamil Nadu, India to evaluate the benefits of growth monitoring. The villages were divided into 6 "growth-monitoring package" of intervention villages (GMP) and 6 "non-growth-monitoring package" of intervention villages (NGM). A functioning primary health care system was in place in all 12 villages. One village nutrition worker in each of the 12 villages implemented a set of interventions including health and nutritional education. About 550 children under the age of 60 months were studied over 4 years in GMP villages and a similar number of children in NGM villages. The interventions were identical in the two sets of villages except for the use of growth charts in education in the 6 GMP villages. The nutrition worker in the NGM villages had the same contact time as in the GMP villages but advised mothers without the benefit of growth charts. The research team, independently of the nutrition worker, did anthropometric studies on children in all villages every 4 to 5 months. Comparisons were done by calculating monthly gains in stature, and weight, and the significance of differences observed was adjusted for age and sex. After 30 months of interventions, similar improvements in growth were seen in GMP and NGM children. The interventions seemed to have improved the nutritional status of young children in both groups of villages. In view of the lack of additional benefit from growth monitoring over other educational interventions, we question its use as part of child survival programmes in India.
Immune complexes from SLE sera induce IL10 production from normal peripheral blood mononuclear cells by an FcgammaRII dependent mechanism: implications for a possible vicious cycle maintaining B cell hyperactivity in SLE
Authors: J Ronnelid
Journal: Annals of the Rheumatic Diseases (2002)

<b>Background:</b> Raised interleukin (IL)6 and IL10 levels are thought to contribute to the pathogenesis of systemic lupus erythematosus (SLE) by enhancing autoantibody production and immune complex (IC) formation. These immune complexes can then stimulate cellular reactions through Fc and complement receptors. <b>Objective:</b> To investigate whether circulating SLE ICs stimulate type 2 cytokine production. <b>Methods:</b> Twenty serum samples from patients with active SLE were compared with sera from 18 healthy controls. Sera and polyethylene glycol (PEG) precipitates from sera were added to peripheral blood mononuclear cell (PBMC) cultures, and the production of IL10 and IL6 was investigated by enzyme linked immunospot assay (ELISPOT) and enzyme linked immunosorbent assay (ELISA). Fc gamma receptor (FcγR) antibodies were used in blocking experiments, and flow cytometry was used to assess the correlation between monocyte FcγR expression and IC-induced cytokine production. <b>Results:</b> Ten per cent dilutions of the SLE sera induced a significantly increased number of IL10-producing cells in comparison with control sera (median, 11.75 <i>v</i> 1.25 spot forming cells/50 000 PBMC; p&lt;0.0001). PEG precipitates from SLE sera also induced significantly increased levels of IL10 (p=0.016) and IL6 (p=0.042) in comparison with control PEG precipitates. IL10 production induced by SLE PEG precipitates or by artificial ICs could be blocked by anti-FcγRII antibodies, and the FcγRII expression on CD14+ monocytes correlated with the IC-induced production of IL10 and IL6. <b>Conclusions:</b> SLE sera stimulate IL10 and IL6 production from PBMC, and this effect is at least partly explained by precipitable ICs acting through FcγRII. This effect provides a possible mechanism for the enhanced production of IL10 in SLE, whereby B cell activation, antibody production, IC stimulated monocytes/macrophages, and type 2 cytokines create a vicious cycle that may help to maintain B cell hyperactivity in SLE.
Gene Transfer of the Na<sup>+</sup>,K<sup>+</sup>-ATPase β1 Subunit Using Electroporation Increases Lung Liquid Clearance
Authors: David Machado-Aranda, Yochai Adir, Jennifer L. Young, Arturo Briva, G. R. Scott Budinger, Anjana V. Yeldandi, Jacob I. Sznajder, David A. Dean
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The development of nonviral methods for efficient gene transfer to the lung is highly desired for the treatment of several pulmonary diseases. We have developed a noninvasive procedure using electroporation to transfer genes to the lungs of rats. Purified plasmid (100-600 microg) was delivered to the lungs of anesthetized rats through an endotracheal tube, and a series of square-wave pulses were delivered via electrodes placed on the chest. Relatively uniform gene expression was observed in multiple cell types and layers throughout the lung, including airway and alveolar epithelial cells, airway smooth muscle cells, and vascular endothelial cells, and this finding was dose- and pulse length-dependent. Most important, no inflammatory response was detected. To demonstrate efficacy of this approach, the beta1 subunit of the Na(+),K(+)-ATPase was transferred to the lungs of rats with or without electroporation, and 3 days later, alveolar fluid clearance was measured. Animals electroporated with the beta1 subunit plasmid showed a twofold increase in alveolar fluid clearance and Na(+),K(+)-ATPase activity as compared with animals receiving all other plasmids, with or without electroporation. These results demonstrate that electroporation is an effective method to increase clearance by introducing therapeutic genes (Na(+),K(+)-ATPase) into the rat lung.
Invariant NKT cells promote alcohol-induced steatohepatitis through interleukin-1β in mice
Authors: Kele Cui, Guoxiu Yan, Congfei Xu, Yongyan Chen, Jun Wang, Rongbin Zhou, Li Bai, Zhexiong Lian, Haiming Wei, Rui Sun, Zhigang Tian
Journal: Journal of Hepatology (2015)
The British Society of Gastroenterology early gastric cancer/dysplasia survey: an interim report.
Authors: F T de Dombal, A B Price, H Thompson, G T Williams, A G Morgan, A Softley, S E Clamp, B J Unwin
Journal: Gut (1990)

This presentation describes interim findings in a series of 319 patients referred from 41 hospitals on the basis of histopathological findings of 9early gastric cancer9, 9dysplasia9, or 9worrying mucosal appearances9. Data were recorded using a predefined proforma, and histopathological material circulated amongst a 9panel9 of three further pathologists. After this process, 132 patients were classified as having early gastric cancer and 63 as dysplasia. There was good agreement between pathologists as to whether the cases had cancer or dysplasia - but 39 cases said by referring pathologists to have early gastric cancer were classified by the panel as having more extensive disease. Most early gastric cancer cases were diagnosed only after histopathological examination. Cancer or 9possible cancer9 was only mentioned after 36% of the radiological investigations and 40.5% of the endoscopies. Computer aided analysis of the patients9 symptoms placed 91.3% of the early gastric cancer cases into a 9high risk9 group - but was unable to distinguish between early gastric cancer and dysplasia. The five year survival rate of the cases agreed to be early gastric cancer by the panel was well over 90%, but the four year survival rate of cases registered as 9early gastric cancer9 but said by the panel to have more advanced disease was under 75%. These findings may account for some of the differences between series, and emphasise the need for precise, widely agreed criteria for the diagnosis of early gastric cancer and gastric dysplasia.
General practitioners and obstetrics: a brief history
Authors: Irvine Loudon
Journal: Journal of the Royal Society of Medicine (2008)

If you had asked an English physician in 1700 about the connection between medicine and midwifery, he would almost certainly have told you that the two had nothing whatsoever to do with each other. Midwifery was an activity confined to uneducated female midwives from which men were rigidly excluded. Occasionally a surgeon was asked to use some kind of surgical instrument in an attempt to deal with an obstructed labour, but that was all.

If, however, you had asked the same question at the end of the 18th century, you would have been told that an increasing number of women were choosing to be delivered at home by medical practitioners, especially the surgeon-apothecaries who were general practitioners in all but name. (It was, by the way, not until the early 19th century that the term ‘obstetrician’ came into common usage, replacing ‘man-midwifery’ and ‘accoucheur’.) By the end of the 18th century it is probable that about half the total deliveries in England and Wales were home deliveries by medical practitioners and the rest by midwives. Only a very small number of deliveries – well under 1% – were delivered in maternity hospitals.1
Lack of Connexin 40 Causes Displacement of Renin-Producing Cells from Afferent Arterioles to the Extraglomerular Mesangium
Authors: Lisa Kurtz, Frank Schweda, Cor de Wit, Wilhelm Kriz, Ralph Witzgall, Richard Warth, Alexander Sauter, Armin Kurtz, Charlotte Wagner
Journal: Journal of the American Society of Nephrology (2007)

In the adult kidney, renin-producing cells are typically located in the walls of afferent arterioles at the transition into the glomerular capillary network. The mechanisms that are responsible for restricting renin expression to the juxtaglomerular position are largely unknown. This study showed that in mice that lack connexin 40 (Cx40), the predominant connexin of renin-producing cells, renin-positive cells are absent in the vessel walls and instead are found in cells of the extraglomerular mesangium, glomerular tuft, and periglomerular interstitium. Blocking macula densa transport function by acute administration of loop diuretics strongly enhances renin secretion in vivo and in isolated perfused kidneys of wild-type mice. This effect of loop diuretics is markedly attenuated in vivo and even blunted in vitro in Cx40-deficient mice. Even after prolonged stimulation of renin secretion by severe sodium depletion, renin expression is not seen in juxtaglomerular cells or in cells of more proximal parts of the arterial vessel wall as occurs normally. Instead, renin remains restricted to the extra-/periglomerular interstitium in Cx40-deficient mice. In contrast to the striking displacement of renin-expressing cells in the adult kidney, renin expression in the vessels of the developing kidney was found to be normal. This is the first evidence to indicate that cell-to-cell communication via gap junctions is essential for the correct juxtaglomerular positioning and recruitment of renin-producing cells. Moreover, these findings support the notion that gap junctions are relevant for the macula densa signaling to renin-producing cells.
The Primary Aromatic Amines: Their Biological Properties and Structure-Activity Relationships
Authors: J L Radomski
Journal: The Annual Review of Pharmacology and Toxicology (1979)

Primary aromatic amines are compounds of considerable industrial and commercial importance. They are used as intermediates in the synthesis of numerous organic compounds including the azo dyes and as antioxidants in consumer goods including most rubber products. Also, they are produced environmentally when plant and other organic material are burned (1). Some aromatic amines have been shown to have potent toxicological prop­ erties. They are one of the classes of substances about which there is much concern from both an occupational and environmental point of view, partic­ ularly with regard to their carcinogenic activity. The continuously rising incidence of bladder cancer among workers in some industries, despite the removal of known carcinogens, highlights the importance of this problem (2). This review is limited to primary aromatic amines specifically excluding the acetamides, such as phenacetin and N,2-fluorenylacetamide, since these substances have been subject to numerous reviews. Aliphatic amines and polyamines, many of which are of considerable biological importance, also are not covered. Unfortunately, many aromatic amines of industrial impor­ tance have not been studied toxicologically, or the toxicity data are not in the open literature. With the current realization that many of these sub­ stances have serious toxic potential, this situation will hopefully be rectified.
A New Level of Complexity
Authors: Thomas Boettger, Thomas Braun
Journal: Circulation Research (2012)

The discovery of the regulatory role of noncoding RNAs, and micro (mi)RNAs in particular, has added a new layer of complexity to our understanding of cardiovascular development. miRNAs regulate and modulate various steps of cardiovascular morphogenesis, cell proliferation, differentiation, and phenotype modulation. miRNAs simultaneously regulate multiple targets, and many miRNAs can bind to the same target, allowing for a complex pattern of regulation of gene expression. miRNA families are continuously added during evolution paralleling the increased complexity of the cardiovascular system in vertebrates compared with invertebrates. Several lines of evidence suggest that the appearance of miRNAs is at least in part responsible for the formation of complex organ systems and stable regulatory mechanisms in vertebrates. We review the current understanding of miRNAs during cardiovascular development. Further progress in this area will help to decipher quantitative changes in gene expression that provide robustness to cellular phenotypes and regulatory options to diseases processes. miRNAs might also provide clues to better understand congenital heart defects, which are the most common birth defects in human newborns.
Effect of ouabain on Na,K-ATPase and electrolyte transport in the dog ileum in vivo.
Authors: N W Read, G J Krejs, V E Jones, J S Fordtran
Journal: Gut (1979)

It is currently believed that the rate and direction of sodium transport in the small intestine may be regulated by the activity of Na,K-ATPase in the basolateral cell membrane. We tested this hypothesis by selectively infusing ouabain, a known inhibitor of Na,K-ATPase, into the mesenteric artery supplying a perfused loop of ileum in 18 dogs. Before ouabain infusion there were significant correlations between the activity of Na,K-ATPase and net and lumen to plasma fluxes of sodium and chloride. After ouabain, there was no significant change in sodium and chloride transport, unidirectional fluxes or transmucosal potential difference, despite a 50% reduction in Na,K-ATPase activity. Furthermore, there was no significant correlation between Na,K-ATPase activity and sodium or chloride transport after ouabain. The only statistically significant effect of ouabain infusion was a reduction in the rate of bicarbonate secretion. Thus, the results of our experiments suggest that mucosal Na,K-ATPase is not a rate-limiting step in the absorption of sodium and chloride in the dog ileum, though it may be an important facilitative factor.
Effect of Exteriorization of the Sheep Fetus on Its Cardiovascular Function
Authors: MICHAEL A. HEYMANN, ABRAHAM M. RUDOLPH
Journal: Circulation Research (1967)

Exteriorized sheep or goat fetuses, with placental circulation continuing, have been extensively used for measurements of fetal cardiovascular function. However, the effects of this procedure on fetal cardiovascular function have not been assessed. We inserted vinyl catheters into an umbilical vein, an umbilical or fetal hindlimb artery, and a hindlimb vein. We measured umbilical arterial and venous blood gas tensions, umbilical blood flow using the steadystate diffusion antipyrine method, and fetal arterial and umbilical venous pressures before and after delivery by cesarean section. Following exteriorization, placental vascular resistance consistently increased and umbilical blood flow decreased. Umbilical venous Po 2 increased, but umbilical arterial and venous pH and Pco 2 and arterial Po 2 did not change significantly. Thus exteriorization of the fetus produces major changes in the fetal circulation, but these changes are not indicated by any major alterations in fetal blood gases and pH.
Comparative Physiology and Pathology of the Skin
Authors: F. R. Bettley
Journal: BMJ (1965)

MCSJO 41 aspects of diagnostic bacteriology, parasit- ology, and cytology are also dealt with in sufficient detail for elementary students.In addition there are brief chapters on the examination of the urine, faeces, and cerebro- spinal fluid.Junior clinical students need short modern introductory books to help them through the maze of modern investigative procedures just as much as they need books on the technique of eliciting and interpretation of "physical signs."Dr. Lock's book fulfils this requirement admirably, and it is to be hoped that the companion volumes dealing with other branches of pathology will achieve the same high standard.
Torsion of the Testis and its Appendages
Authors: R. H. Chapman, A. J. Walton
Journal: BMJ (1972)

In a survey of 101 cases with an index diagnosis of torsion of the testis or its appendage, there were 86 instances of torsion of the testis and 14 of torsion of the hydatid of Morgagni. In 38 of the patients with testicular torsion there were one or more "warning" attacks of pain and swelling, due to torsion which became spontaneously untwisted. In 19 cases operative fixation was performed because of this warning history, and all the testes were preserved. In the other 19 the testes were not explored until the patient came in with a severe "classical" episode of torsion: seven of these testicles were lost from gangrene or delayed atrophy.In 31 cases torsion resulted in failure to save the testis. Of these, 20 were misdiagnosed and treated initially as epididymo-orchitis, despite there being no evidence of a urinary tract infection. There is no excuse for not exploring any actuely inflammed testicle which is unaccompanied by definite evidence of urinary or urethral infection.