tbuckley/cabot-search huggingface dataset:
Prognostic algorithm identified in node-negative early breast cancer patients predicts outcome also in node-positive patients treated with adjuvant chemotherapy.
Authors: R Kronenwett, KT Kalogeras, U Stropp, K Weber, U Dafni, M Gehrmann, D Pectasides, C von Toerne, P Papakostas, RM Wirtz, G Fountzilas
Journal: Cancer Research (2009)

Abstract Abstract #6044 Background: Recently, we identified and validated a prognostic multigene score, which predicted outcome in early node-negative breast cancer patients that did not receive systemic therapy. The aim of this study was to examine the performance of our prognostic multigene algorithm in node-positive patients treated with adjuvant chemotherapy.&amp;#x2028; Patients and Methods: Patients were treated with adjuvant anthracycline-based chemotherapy in the context of a randomized Phase III study. This was a two-arm trial (E-CMF vs. E-T-CMF) investigating postoperative dose-dense sequential chemotherapy with epirubicin (E) followed by CMF with or without paclitaxel (T). RNA was isolated from 222 formalin-fixed, paraffin-embedded tumor tissue samples, using a Siemens proprietary automated method based on silica-coated magnetic beads, followed by kinetic one-step RT-PCR for mRNA expression analysis of 9 informative genes and 2 normalization genes. For each patient a risk score was calculated using a linear combination of expression values. Patients were separated into high, intermediate and low risk by applying two thresholds of the score. As used in node-negative patients, distant metastasis-free survival (MFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using the log-rank test. Cox analysis for MFS and OS was also performed.&amp;#x2028; Results: The prognostic score could be calculated for 213 patients (102 E-T-CMF; 111 E-CMF). Looking at all patients independently of type of chemotherapy, the score could classify the patients into three distinct risk groups, which were significantly different in terms of MFS (log-rank test, p=0.004) and OS (p=0.01). The separation of the risk groups was even better when focusing on patients with more than three involved lymph nodes (MFS: p=0.0001; OS: p=0.0015; n=166). The respective analysis of the two treatment arms showed that the separation of the risk groups was only significant in E-CMF-treated patients (E-CMF: p=0.002; E-T-CMF: p=0.37). Interestingly, the subgroup of patients with more than three involved lymph nodes and classified as intermediate or high risk (n=77) had a nearly significant better MFS when treated with E-T-CMF in comparison with E-CMF (p=0.07; HR: 0.53; 95% CI: 0.2685 to 1.060).&amp;#x2028; Conclusions: Our prognostic algorithm, identified and validated in node-negative patients that had not been systemically treated, predicts outcome also in node-positive chemotherapy-treated patients. Our findings suggest that the prognostic score may also be predictive of benefit from the addition of taxanes to adjuvant chemotherapy. This hypothesis needs to be confirmed in a larger cohort of samples from an independent clinical study. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6044.
Antibiotic Activity in Urine and Feces after Oral and Intravenous Administration of Demethylchlortetracycline
Authors: William M. Sweeney, A. C. Dornbush, Stanton M. Hardy
Journal: New England Journal of Medicine (1960)

DEMETHYLCHLORTETRACYCLINE (DMCT), a new antibiotic described by McCormick et al.,1 has been the subject of extensive clinical pharmacologic studies.2 3 4 5 6 7 The absorption after oral administration, excretion in urine and bile, plasma protein binding, renal clearance and distribution volume have been measured and compared with previously known tetracycline compounds. Furthermore, investigation has shown that the drug has a sustained antimicrobial activity in the serum after administration by both oral and intravenous routes.2 , 3 , 5 In separate studies, Kunin and Finland4 , 5 have demonstrated that 40 per cent of intravenously administered demethylchlortetracycline was recovered in urine and that concentrations exceeding thirty times the serum concentrations were . . .
Cellular basis of skin allograft rejection across a class I major histocompatibility barrier in mice depleted of CD8+ T cells in vivo.
Authors: A S Rosenberg, T I Munitz, T G Maniero, A Singer
Journal: The Journal of Experimental Medicine (1991)

The present study was undertaken to define the cellular mechanisms involved in the rejection of major histocompatibility complex (MHC) class I disparate skin grafts by mice depleted of CD8+ T cells in vivo. Mice were effectively depleted of CD8+ T cells by adult thymectomy followed by in vivo administration of anti-CD8 monoclonal antibody (mAb) and then engrafted with allogeneic skin. We found that CD8 depleted mice did reject MHC class I disparate skin grafts, but only when the grafts also expressed additional alloantigens. Despite the marked depletion of CD8+ T cells in these mice, we found that their rejection of MHC class I disparate grafts was mediated by CD8+ cytolytic T lymphocyte (CTL) effectors that had escaped depletion. These CD8+ CTL effectors were unique in that: (a) their generation was dependent upon the injected anti-CD8 mAb and upon exposure to class I MHC alloantigens expressed on the engrafted skin, and (b) their effector function was resistant to blockade by anti-CD8 mAb. We observed that the additional alloantigens coexpressed on MHC class I disparate grafts that triggered graft rejection in CD8-depleted mice could be MHC-linked or not and that they functioned in these rejection responses to activate third party specific CD4+ T helper (Th) cells to provide helper signals for the generation of CD8+ anti-CD8 resistant CTL effector cells. Thus, mice depleted of CD8+ T cells by thymectomy and in vivo administration of anti-CD8 mAb harbor a unique population of anti-CD8 resistant, CD8+ effector cells that mediate anti-MHC class I responses in vivo and in vitro, but require help from third party specific Th cells to do so.
Thiol redox disturbances in children with severe asthma are associated with posttranslational modification of the transcription factor nuclear factor (erythroid-derived 2)–like 2
Authors: Anne M. Fitzpatrick, Susan T. Stephenson, Graham R. Hadley, Leandrea Burwell, Madhuri Penugonda, Dawn M. Simon, Jason Hansen, Dean P. Jones, Lou Ann S. Brown
Journal: Journal of Allergy and Clinical Immunology (2011)
POINTS FROM LETTERS: Incubation of Chicken-pox
Authors: L. Potter
Journal: BMJ (1952)

<b>Introduction:</b> Alpha 1 antitrypsin deficiency (A1ATD) as an etiology for bronchiectasis has been a target of discussion. Several cases have been described but large studies are scarce. <b>Aims:</b> Characterize a group of patients with A1ATD and bronchiectasis and establish a cause-effect relation between the two. <b>Methods:</b> Within a total of 110 patients with A1ATD followed in the outpatient department between 2012-14, we selected patients that presented imagiological evidence of bronchiectasis. Clinical and analytical parameters were assessed. The bronchiectasis classification - <i>Bronchiectasis Severity Index</i> (BSI) was used. <b>Results:</b> 26 patients met the inclusion criteria. Mean value of A1AT 59.9 mg/dl. ZZ phenotype was the most prevalent (42.3%). Pulmonary emphysema was present in 53.8%. Bronchiectasis were bilateral in 73,1% and with involvement of 2 pulmonary lobes in 50%. Most of the patients showed mild bronchiectasis (57.7%), with a minority of severe cases (19.2%). There was a correlation between the severity of A1ATD and bronchiectasis, with a preponderance of the phenotype ZZ (100%) within the group with most severe cases. When accessing patients with phenotype ZZ <i>versus</i> other phenotypes concerning the BSI, there was a positive and statistically significant association. The patients ZZ presented a higher rate of infectious exacerbations, hospital admissions and colonization by <i>Pseudomonas aeruginosa</i>. The clinical severity illustrated by the BSI seems to be independent of emphysema. <b>Conclusions:</b> This study shows an association between A1ATD phenotypes and bronchiectasis severity, independent of the presence of emphysema. This link can be important not only in terms of diagnosis but also concerning a therapeutic strategy.
Role of thyroid hormone in postnatal circulatory and metabolic adjustments.
Authors: J A Breall, A M Rudolph, M A Heymann
Journal: Journal of Clinical Investigation (1984)

To assess the role of the early postnatal surge in plasma thyroid hormone concentrations on cardiovascular and metabolic adaptations, we measured cardiac output, total oxygen consumption, and plasma triiodothyronine (T3) concentrations in three groups of lambs in the first 6 h after delivery. 15 fetal lambs were prepared at gestational ages of 128-129 d by placing catheters in the brachiocephalic artery, descending aorta, distal inferior vena cava, left atrium, and pulmonary artery so that measurements could be made soon after delivery. They were divided into three groups: Group I comprised five control animals; Group II consisted of five fetuses in which thyroidectomy was performed at surgery at 129 d gestation; and Group III consisted of five animals in which thyroidectomy was performed at term gestation during delivery by caesarian section, prior to severing the umbilical cord. The lambs in Group I exhibited a rapid postnatal rise in T3 concentrations, similar to that described previously, reaching a peak value of about 5 ng/ml. Although the postnatal surge in T3 concentration was arrested in Group II and III animals, Group II had no detectable plasma T3, while the Group III animals had T3 concentrations of about 0.8 ng/ml, which were within the range previously reported for term lamb fetuses. The lambs in group II showed 40-50% lower left ventricular outputs (190 vs. 297 ml/kg per min), systemic blood flows (155 vs. 286 ml/kg per min), and oxygen consumptions (9.8 vs. 20.2 ml/kg per min) as compared with Group I animals over the entire 6-h period. The lambs in Group II also had significantly lower heart rates (131 vs. 192 beats/min) and mean systemic arterial pressures (56 vs. 72 torr). However, there were no significant differences for any of these measurements between the Group III and Group I lambs. The reduction in cardiac output in the Group II animals were reflected in a significantly lower blood flow to the peripheral circulation, but there were no significant differences in blood flow to other organs in the three groups. These studies indicate that plasma thyroid concentrations in the 2-3 wk prior to delivery and not the increase in thyroid hormone concentrations which occur after birth are important for postnatal cardiovascular and metabolic adjustments. We speculate that lack of circulating triiodothyronine in late gestation may affect postnatal cardiovascular adaptation by modifying normal beta adrenergic receptor development.
Localisation and differential expression of the fibroblast growth factor receptor (FGFR) multigene family in normal and atherosclerotic human arteries
Authors: S. E. Hughes
Journal: Cardiovascular Research (1996)

Aberrant expression of FGF-1 and FGF-2 may be central to the atherosclerotic disease process, promoting both intimal hyperplasia and plaque neovascularisation. FGF-1 and FGF-2 mediate their biological effects by binding to a family of specific high-affinity cell surface receptors with protein tyrosine kinase activity. Four receptors have been identified in the human (FGFR1/flg gene product, FGFR2/bek gene product, FGFR3 and FGFR4), but little is known of their in vivo tissue distribution. Characterisation of the spatial distribution of the FGFR multigene family in both normal and atherosclerotic arteries is a prerequisite to further define the functional role of FGF-1 and FGF-2 in atherosclerosis. The objective of this study was to examine the cell-type-specific expression of the FGFR multigene family members in both normal and atherosclerotic human arteries.FGFR expression was investigated immunocytochemically with polyclonal antisera to FGFR1-4 and by in situ hybridisation using FGFR1-4 riboprobes in archival material. Total cellular mRNA was analysed using poly d(T) and the levels correlated with the expression of FGFR1-4 mRNA.At the protein level, FGFR1-4 were expressed in the medial smooth muscle cells and adventitial vessels of normal arteries. In simple and advanced lesions, the expression profiles of FGFR1-4 showed variability between individual arteries, and cell-type-specific differential FGFR expression was apparent. Widespread co-expression of FGFR1 and FGFR2 was observed in intimal smooth muscle cells, foam cells and the plaque microvasculature of simple and advanced lesions. FGFR3 and FGFR4 exhibited more restricted patterns of distribution within the plaque. In situ hybridisation with poly d(T) confirmed high cellular transcriptional activity in archival atherosclerotic lesions. The high levels of total cellular mRNA and FGFR protein were not always reciprocated at the FGFR1-4 mRNA level, and only FGFR1 and FGFR2 mRNA transcripts were abundant in intimal lesions.These data provide evidence to suggest involvement of the FGF-FGFR multigene families in human atherogenesis. Differential FGFR expression in plaque subtypes may reflect distinct differences in receptor function which may be relevant to lesion progression during atherosclerosis.
Pneumoperitoneum without faecal peritonitis in a patient with pseudomembranous colitis.
Authors: D Klinger, P Radford, J Callin
Journal: BMJ (1984)

Une observation tres rare: colite pseudomembraneuse chez une malade ayant recu des antibiotiques prophylactiques a l'occasion d'une prothese de hanche. La malade presente un pneumoperitoine sans peritonite. L'explication serait une transsudation de gaz mais non de liquides a travers les parois coliques tres amincies mais non perforees
A viable alternative to null-hypothesis testing
Authors: Bruno D. Zumbo
Journal: Behavioral and Brain Sciences (1998)

This commentary advocates an alternative to null-hypothesis testing that was originally represented by Rozeboom over three decades ago yet is not considered by Chow (1996). The central distinguishing feature of this approach is that it allows the scientist to conclude that the data are much better fit by those hypotheses whose values fall inside the interval than by those outside.
QUININ AND IRON IN PNEUMONIA.
Authors: CHARLES F. NIEDER
Journal: JAMA (1905)

The results obtained by Dr. Galbraith,<sup>1</sup>of Sonora, Mex., in the treatment of pneumonia by the use of large doses of quinin sulphate and of the tincture of the chlorid of iron, as shown by the effect on the temperature, pulse and circulation, seemed to be of even greater importance than the fact that he had treated fifty consecutive cases without a death. Since reading Dr. Galbraith's last article I have treated six patients with lobar pneumonia in like manner, with very satisfactory results in every case. <h3>Case 1.</h3> —J. H., aged 46, laborer, was taken ill March 8, 1905. He complained of severe headache and pain in the right side of the chest. <h3>Examination.</h3> —Temperature, 102; pulse, 96; respiration, 28. Percussion of chest was negative. Breath sounds were suppressed on the right side. On March 9, at 10 a. m., temperature was 104.6; pulse, 120; respiration, 36. Percussion
Insulin-Induced Lipoatrophy in Type I Diabetes: A possible tumor necrosis factor-α-mediated dedifferentiation of adipocytes
Authors: Catherine Atlan-Gepner, Pierre Bongrand, Catherine Farnarier, Luc Xerri, Régine Choux, Jean-Francois Gauthier, Thierry Brue, Philippe Vague, Jean-Jacques Grob, Bernard Vialettes
Journal: Diabetes Care (1996)

To test the hypothesis that tumor necrosis factor (TNF)-alpha may mediate the loss and the dedifferentiation of subcutaneous fat tissue in the insulin-induced lipoatrophies of a diabetic patient who presented extensive lesions.An in vitro exploration of cytokine production by peripheral blood mononuclear cells (PBMC) from the reported case was performed and compared with the same explorations of PBMC from three nondiabetic subjects and three diabetic patients without lipoatrophic lesions. A proliferation test and an evaluation of TNF-alpha and interleukin (IL)-6 production from PBMC in presence of insulin were studied.The production of TNF-alpha and IL-6 by the macrophages of the patient in presence of insulin were dramatically increased in comparison with control subjects. This process needed cooperation with other lymphoid cells and was abrogated by dexamethasone.In our reported case, a local hyperproduction of TNF-alpha from macrophages that was induced by the injected insulin could explain the dedifferentiation of the adipocytes of the subcutaneous tissue and the reversion that was induced by the local injection of dexamethasone.
A newly identified group of adolescents at “invisible” risk for psychopathology and suicidal behavior: findings from the SEYLE study
Authors: Vladimir Carli, Christina W. Hoven, Camilla Wasserman, Flaminia Chiesa, Guia Guffanti, Marco Sarchiapone, Alan Apter, Judit Balazs, Romuald Brunner, Paul Corcoran, Doina Cosman, Christian Haring, Miriam Iosue, Michael Kaess, Jean Pierre Kahn, Helen Keeley, Vita Postuvan, Pilar Saiz, Airi Varnik, Danuta Wasserman
Journal: World Psychiatry (2014)

This study explored the prevalence of risk behaviors (excessive alcohol use, illegal drug use, heavy smoking, reduced sleep, overweight, underweight, sedentary behavior, high use of Internet/TV/videogames for reasons not related to school or work, and truancy), and their association with psychopathology and self-destructive behaviors, in a sample of 12,395 adolescents recruited in randomly selected schools across 11 European countries. Latent class analysis identified three groups of adolescents: a low-risk group (57.8%) including pupils with low or very low frequency of risk behaviors; a high-risk group (13.2%) including pupils who scored high on all risk behaviors, and a third group ("invisible" risk, 29%) including pupils who were positive for high use of Internet/TV/videogames for reasons not related to school or work, sedentary behavior and reduced sleep. Pupils in the "invisible" risk group, compared with the high-risk group, had a similar prevalence of suicidal thoughts (42.2% vs. 44%), anxiety (8% vs. 9.2%), subthreshold depression (33.2% vs. 34%) and depression (13.4% vs. 14.7%). The prevalence of suicide attempts was 5.9% in the "invisible" group, 10.1% in the high-risk group and 1.7% in the low-risk group. The prevalence of all risk behaviors increased with age and most of them were significantly more frequent among boys. Girls were significantly more likely to experience internalizing (emotional) psychiatric symptoms. The "invisible" group may represent an important new intervention target group for potentially reducing psychopathology and other untoward outcomes in adolescence, including suicidal behavior.
Laboratory-Based Surveillance of Salmonella Serotype Typhi Infections in the United States
Authors: Marta-Louise Ackers, Nancy D. Puhr, Robert V. Tauxe, Eric D. Mintz
Journal: JAMA (2000)

Multidrug-resistant Salmonella serotype Typhi infections have been reported worldwide, but data on the incidence of resistant strains in the United States are lacking.To determine the incidence of antimicrobial-resistant Salmonella Typhi infections and to identify risk factors for infection.Cross-sectional laboratory-based surveillance study.A total of 293 persons with symptomatic typhoid fever who had Salmonella Typhi isolates and epidemiological information submitted to US public health departments and laboratories from June 1, 1996, to May 31, 1997.Proportion of Salmonella Typhi isolates demonstrating resistance to 12 antimicrobial agents; patient epidemiological factors associated with drug-resistant infections.Median age was 21 years (range, 3 months to 84 years); 56% were male. Two hundred twenty-eight (80%) were hospitalized; 2 died. In the 6 weeks before illness onset, 81% of patients had traveled abroad. Seventy-four Salmonella Typhi isolates (25%) were resistant to 1 or more antimicrobial agent, and 51 (17%) were resistant to 5 or more agents, including ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant Salmonella Typhi [MDRST]). Although no resistance to ciprofloxacin or ceftriaxone was observed, 20 isolates (7%) were nalidixic acid-resistant (NARST). Patients with MDRST and NARST infections were more likely to report travel outside the United States, particularly to the Indian subcontinent (Bangladesh, India, and Pakistan) (odds ratio [OR], 29.3; 95% confidence interval [CI], 6.8-126.7; P<.001 and OR, 35.9; 95% CI, 3.4-377.3; P<.001, respectively).Our data suggest that ciprofloxacin and ceftriaxone are appropriate empirical therapy for suspected typhoid fever; however, resistance may be anticipated. Continued monitoring of antimicrobial resistance among Salmonella Typhi strains will help determine vaccination and treatment policies. JAMA. 2000;283:2668-2673.
Conference plans reconstruction of Darfur's health services in wake of ceasefire
Authors: P. Moszynski
Journal: BMJ (2010)

Darfur’s main rebel group signed a truce with Sudan’s government this week, paving the way for a negotiated end to a conflict that has displaced millions of people and devastated the region. This “potential breakthrough” makes next week’s London conference on rebuilding Darfur’s shattered health services “exceptionally timely,” says its organiser, Mohamed Baraka.

Being held at London University’s School of Oriental and African Studies from 1 March to 3 March, the conference is organised by the charity British Friends of Sudan, in collaboration with the Sudanese community based development agency Development Action Now, Sudan’s Ahfad University for Women, and the London Middle East Institute.

Professor Baraka told the BMJ , …
Abstract 15185: Vascular Endothelial Growth Factor Inhibition Results in Systemic Hypertension Mediated by Alterations in Endothelin-1, but Not by Alterations in Nitric Oxide or Reactive Oxygen Species
Authors: Vincent J de Beer, Mariette H Kappers, Zhichao Zhou, Anton H van den Meiracker, A.H. J Danser, Stefan Sleijfer, Dirk J Duncker, Daphne Merkus
Journal: Circulation (2011)

Purpose:  Inhibition of Vascular Endothelial Growth Factor (VEGF) signaling is an established therapy for various forms of cancer. However, this therapy is associated with hypertension. VEGF signaling enhances NO production, which in turn may reduce endothelin (ET) and scavenge reactive oxygen species (ROS). We therefore hypothesized that hypertension resulting from VEGF inhibition is due to a loss of NO bioavailability and an increase in ROS and/or ET.   Methods:  On different days, chronically instrumented swine (N=6) received i.v. infusion of either the endothelial NO synthase inhibitor N ω -Nitro-L-arginine (NLA), the ET A /ET B  receptor blocker tezosentan or a combination of ROS scavengers (4-Hydroxy-2,2,6,6-Tetramethylpiperidine-1-oxyl, N-Acetyl-Cysteine and N-2-Mercaptoproprionyl-Glycine). Before and after these infusions hemodynamic parameters were recorded. These experiments were repeated after administration of the VEGF-receptor inhibitor sunitinib, 50 mg/day p.o. for 1 week.   Results:  Sunitinib increased blood pressure and systemic vascular resistance reflecting vasoconstriction (Table). Following sunitinib, the rise in blood pressure and systemic vascular resistance induced by NLA increased, while the changes in blood pressure by ROS scavenging decreased. In contrast, while tezosentan had no effect under control conditions, it resulted in a decrease in blood pressure and systemic vascular resistance following sunitinib. Hence, tezosentan abrogated the sunitinib-induced vasoconstriction.   Conclusions:  VEGF inhibition results in sustained hypertension. This hypertension is caused by enhanced ET-mediated vasoconstriction, but not by decreased NO-bioavailability or enhanced oxidative stress. These results warrant studies into the efficacy of ET receptor blockade in limiting the hypertensive side effects of VEGF inhibition.