tbuckley/cabot-search huggingface dataset:
Long-term safety and asthma control measures with a budesonide/formoterol pressurized metered-dose inhaler in African American asthmatic patients: A randomized controlled trial
Authors: Randall W. Brown, Christopher D. O'Brien, Ubaldo J. Martin, Tom Uryniak, Kathy L. Lampl
Journal: Journal of Allergy and Clinical Immunology (2012)

Information surrounding the long-term safety of combination inhaled corticosteroid/long-acting β(2)-adrenergic agonist medications in African American asthmatic patients is limited.We sought to assess safety and asthma control with a budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus budesonide over 1 year in African American patients.This 52-week, randomized, double-blind, parallel-group, multicenter, phase 3B safety study (NCT00419952) was conducted in 742 self-reported African American patients 12 years or older with moderate-to-severe asthma previously receiving medium- to high-dose inhaled corticosteroids. After 2 weeks using a 320 μg twice-daily budesonide pMDI, patients were randomized 1:1 to 320/9 μg twice-daily budesonide/formoterol pMDI or 320 μg twice-daily budesonide pMDI.Both treatments were well tolerated. Asthma exacerbation incidence and rate (per patient-treatment year) were lower with budesonide/formoterol versus budesonide (incidence, 7.7% vs 14.0% [P= .006]; rate ratio, 0.615 [P= .002]). Time to first asthma exacerbation was longer (P= .018) with budesonide/formoterol versus budesonide. The most common adverse events, regardless of study drug relationship, were headache (9.5% and 7.7%), nasopharyngitis (6.9% and 8.0%), sinusitis (4.0% and 6.3%), and viral upper respiratory tract infection (5.8% and 4.4%) for budesonide/formoterol and budesonide, respectively. Serious adverse events occurred in 12 and 15 patients, respectively; none were considered drug related. No substantial or unexpected patterns of abnormalities were observed in laboratory, electrocardiographic, or Holter monitoring assessments. Hospitalization caused by asthma exacerbation occurred in 0 and 4 patients in the budesonide/formoterol and budesonide groups, respectively. Pulmonary function and asthma control measures generally favored budesonide/formoterol.In this population budesonide/formoterol pMDI was well tolerated over 12 months, with a safety profile similar to that of budesonide; the asthma exacerbation rate was reduced by 38.5% versus budesonide.
IB-11 * PSEUDO-PROGRESSION (PsdPg) IS A HARBINGER OF A MORE EFFECTIVE ANTI-TUMOR RESPONSE
Authors: L. Sturla, J. Donahue, J. Machan, S. Delamonte, S. Jeyapalan
Journal: Neuro-Oncology (2014)

BACKGROUND: PsdPg is the increased contrast enhancement, high choline/creatine ratio and increased perfusion observed in the residual tumor bed of high-grade glioma patients after completion of temozolomide/radiation. It resolves within 3-6 months and incidence ranges from 10 - 31%. Though correlated with longer patient survival, its pathological basis is unclear. We used a cytokine/chemokine focused approach to compare the tumor microenvironment in pre- and post-treatment tumor tissue from patients with PsdPg to patients with true progression (TP). METHODS: We obtained pre-treatment formalin fixed paraffin embedded (FFPE) tissue from 35 GBM patients and post-treatment FFPE tissue from five patients with PsdPg and TP. A quantitative PCR array and custom Quantigene 2.0 multiplex was used to quantify gene expression corresponding to major cytokines/chemokines. An 18-gene signature was used to determine the macrophage polarization score (cumulative M2-associated cytokine expression - cumulative M1-associated cytokine expression). Immunohistochemistry (IHC) was used to confirm significantly different targets at the protein level. RESULTS: IHC revealed 7-fold higher B-cell infiltration in TP patients as compared to patients with PsdPg (p = 0.003). Macrophage and T-cell infiltration were not significantly different between the two groups. Nevertheless, the cytokines associated with macrophage polarization indicated pro-tumorigenic (M2) polarization in TP patients while PsdPg patients exhibited classical anti-tumorigenic (M1) polarization. TP patients had a 10-fold higher M2 score (p = 0.03) compared to PsdPg patients. The M1 score of tissue from PsdPg patients post-treatment was 25-fold higher than their pre-treatment tissue (p = 0.01). Analysis of a 7-gene signature associated with natural killer (NK) cell recruitment and activation showed a 8-fold higher expression in pre-treatment tissue from PsdPg patients compared to TP patients (p = 0.009) suggesting that NK cells, which are mediators of anti-tumor immunity, play an important role in pseudo-progression. CONCLUSIONS: These data suggest a more effective anti-tumor immune response in PsdPg patients, which may explain their longer overall survival.
Distribution of metallothionein-bound cadmium and cadmium chloride in mice: preliminary studies.
Authors: M Nordberg, G F Nordberg
Journal: Environmental Health Perspectives (1975)

Metallothionein from livers of mice was isolated by gel chromatography and isoelectric focusing. One of two forms thus obtained contained 32 percent cysteine. This form, labeled in vitro with 109Cd, was injected intravenously in mice, and the distribution of 109Cd was studied. Animals killed after 4 hrs had over 80 percent of the injected dose in the kidneys. Protein obtained after gel chromatography, containing both forms of cadmium-binding protein, was also labeled in vitro with 109Cd and injected intravenously. Animals killed 4 hrs after injection had 50 percent of the injected dose in the kidneys. Whole-body measurements and wholebody autoradiography demonstrated that approximately 40-60 percent of the injected dose had been excreted in urine. The results show a selective accumulation of metallothionein-bound cadmium in the kidney and indicate possible differences in distribution and excretion of cadmium depending on binding to different forms of low molecular weight cadmium-binding proteins.
Quantitative trait loci associated with susceptibility to therapy-related acute murine promyelocytic leukemia in hCG-PML/RARA transgenic mice
Authors: Ryan K. Funk, Taylor J. Maxwell, Masayo Izumi, Deepa Edwin, Friederike Kreisel, Timothy J. Ley, James M. Cheverud, Timothy A. Graubert
Journal: Blood (2008)
Measles Virus Entry Through the Signaling Lymphocyte Activation Molecule Governs Efficacy of Mantle Cell Lymphoma Radiovirotherapy
Authors: Tanner S Miest, Marie Frenzke, Roberto Cattaneo
Journal: Molecular Therapy (2013)

We developed here a vaccine-identical measles virus (MV) as an oncolytic agent against mantle cell lymphoma (MCL), an aggressive B-cell non-Hodgkin's lymphoma that is difficult to cure but radiosensitive. We armed the virus with the sodium-iodide symporter, which concentrates iodide within infected cells enabling noninvasive imaging and combination radiovirotherapy. Through high-resolution in vivo and ex vivo imaging, we visualized the spread of infections in primary and metastatic tumors for over 2 weeks after therapy, documenting homogeneous virus seeding and spread restricted to perfused tissue. Infection of metastases was more rapid and intense than primary tumors, achieving isotope uptake within about threefold the efficiency of the thyroid. Virotherapy combined with systemic (131)I resulted in more rapid disease regression than either therapy alone. In addition to ubiquitous CD46, vaccine MV retains cell entry through its immune cell-specific receptor signaling lymphocytic activation molecule (SLAM). We asked whether both receptors could sustain effective oncolysis of MCL. Strikingly, only SLAM-dependent entry sustained efficient viral spread, tumor regression, and prolonged survival. These observations shift the focus of future clinical trials to SLAM-expressing hematologic malignancies and suggest that oncolytic vectors may depend on tissue-specific receptors for both cell entry and activation of responses assisting their replication.
1079. Successful Myoblast Transplantation to Duchenne Muscular Dystrophy Patients
Authors: Jacques P. Tremblay, Daniel Skuk, Sylvain Michel, Raynald Roy, Jean-Guy Lachance, Hélène Senay, Deschênes Louise, Goulet Marlyne, Brigitte Roy, Jean-Pierre Bouchard
Journal: Molecular Therapy (2005)

Nine Duchenne muscular dystrophy (DMD) patients received injections of myoblasts obtained from skeletal muscle biopsies of normal donors. Cells were injected in 1 cm3 of the Tibialis anterior by 25 or 100 parallel injections. We performed similar patterns of saline injections in the contralateral muscles as controls. The patients received tacrolimus for immunosuppression. Muscle biopsies were performed at the injected sites 4 weeks later. We observed dystrophin-positive myofibers in the cell-grafted sites: in 8 of of 9 patients. In these 8 patients, the percentages of dystrophin positive fibers ranged from 3.5 to 26%. Eight patients had identified dystrophin-gene deletions and thus for four of these patients these results were obtained using mAbs specifically to epitopes coded by the deleted exons. Donor-dystrophin was absent in the control sites. For the other patients there were several folds more dystrophin-positive myofibers in the cell-grafted muscle than in the control muscle. Donor-dystrophin transcripts were detected by RT-PCR (using one primer reacting with a sequence in the deleted exons) in 8 patients. No antibodies were detected in the host serum against the donor myoblasts. Therefore, significant dystrophin expression can be obtained in the skeletal muscles of DMD patients following specific conditions of cell delivery and immunosuppression.
A quarter of consultants ready to resign over new contract, says BMA
Authors: S. Hargreaves
Journal: BMJ (2003)

An estimated 7000 NHS consultants will resign or retire from the service if national negotiations cannot resolve the current dispute over their contract, according to details of a BMA survey released this week.

The threat came in response to a decision by Alan Milburn, the health secretary, to hold no further national negotiations on the consultant contract after BMA members rejected a deal in October. The questionnaire responses, received from 11000 of 27852 consultants in England, found that nine out of 10 consultants would be willing to take some sort of action if deadlock is reached, ranging from lobbying activity through to working to contract or resigning from the …
Regulation of the last two enzymatic reactions in cholesterol biosynthesis in rats: Effects of BM 15.766, cholesterol, cholic acid, lovastatin, and their combinations
Authors: A Honda, S Shefer, G Salen, G Xu, A K Batta, G S Tint, M Honda, T C Chen, M F Holick
Journal: Hepatology (1996)

The Smith–Lemli–Opitz syndrome is a common inherited birth disorder caused by markedly reduced 7–dehydrocholesterol δ7–reductase activity, the final enzyme in the cholesterol biosynthetic pathway. BM 15.766 (4–[2–[1–(4–chlorocinnamyl)piperazin–4–yl]ethyl]–benzoic acid) inhibits 7–dehydrocholesterol delta 7–reductase activity, reduces plasma cholesterol levels, and increases 7–dehydrocholesterol levels to reproduce the biochemical abnormalities of the syndrome in rats. Cholesterol, cholic acid, and lovastatin, alone or in combinations, were fed to rats given BM 15.766, and hepatic activities of the last two enzymes in the cholesterol biosynthetic pathway, lathosterol 5– dehydrogenase and 7–dehydrocholesterol delta 7–reductase, were measured. After feeding BM 15.766, hepatic 7–dehydrocholesterol delta 7–reductase activity decreased by 77% while lathosterol 5–dehydrogenase activity tended to increase, so that the ratio of 5–dehydrogenase to delta 7–reductase activities increased from 0.33 to 2.8. In BM 15.766– fed rats, treatment with cholesterol suppressed both 5–dehydrogenase and delta 7–reductase activities by 76% and 66%, respectively, and decreased the 5–dehydrogenase: delta 7–reductase activities ratio from 2.8 to 2.2. In contrast, treatment with cholic acid and BM 15.766 further inhibited delta 7–reductase activity by 67% without changing significantly the 5–dehydrogenase activity that had increased the ratio to 5.5. Combining BM 15.766 with lovastatin increased 5–dehydrogenase activity fivefold but did not change delta 7–reductase activity, raising the ratio to 14.3. In BM 15.766–treated rats, the first and last two enzymatic reactions in the cholesterol biosynthetic pathway catalyzed by 3–hydroxy–3–methylglutaryl coenzyme A (HMG–CoA) reductase, lathosterol 5–dehydrogenase, and 7–dehydrocholesterol delta 7–reductase are down–regulated by cholesterol. Thus, only cholesterol and not cholic acid or lovastatin could reduce elevated plasma 7– dehydrocholesterol levels induced by BM 15.766.
How Can We Tell When Cancer Vaccines Vaccinate?
Authors: Jedd D. Wolchok, Paul B. Chapman
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.12.065 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12586792 How Can We Tell When Cancer Vaccines Vaccinate? Jedd D. WolchokxJedd D. WolchokSearch for articles by this author , Paul B. ChapmanxPaul B. ChapmanSearch for articles by this author Show More Memorial Sloan-Kettering Cancer Center, New York, NY https://doi.org/10.1200/JCO.2003.12.065 Full Text PDF Figures and Tables "How Can We Tell When Cancer Vaccines Vaccinate?." Journal of Clinical Oncology, 21(4), pp. 586–587© 2003 by American Society of Clinical Oncology
Clinical findings for the first 1000 Gulf war veterans in the Ministry of Defence's medical assessment programme
Authors: W J Coker, B M Bhatt, N F Blatchley, J T Graham
Journal: BMJ (1999)

To review the clinical findings in the first 1000 veterans seen in the Ministry of Defence's Gulf war medical assessment programme to examine whether there was a particular illness related to service in the Gulf.Case series of 1000 veterans who presented to the programme between 11 October 1993 and 24 February 1997.Gulf war veterans.Diagnosis of veterans' conditions according to ICD-10 (international classification of diseases, 10th revision). Cases referred for psychiatric assessment were reviewed for available diagnostic information from consultant psychiatrists.588 (59%) veterans had more than one diagnosed condition, 387 (39%) had at least one condition for which no firm somatic or psychological diagnosis could be given, and in 90 (9%) veterans no other main diagnosis was made. Conditions characterised by fatigue were found in 239 (24%) of patients. At least 190 (19%) patients had a psychiatric condition, which in over half was due to post-traumatic stress disorder. Musculoskeletal disorders and respiratory conditions were also found to be relatively common (in 182 (18%) and 155 (16%) patients respectively).Many Gulf war veterans had a wide variety of symptoms. This initial review shows no evidence of a single illness, psychological or physical, to explain the pattern of symptoms seen in veterans in the assessment programme. As the veterans assessed by the programme were all self selected, the prevalence of illness in Gulf war veterans cannot be determined from this study. Furthermore, it is not known whether the veterans in this study were representative of sick veterans as a group.
HERNIA OF THE BLADDER AS A COMPLICATION OF INGUINAL HERNIA
Authors: G. B. Ferguson
Journal: BMJ (1903)

within twelve hours of perforation and found a small opening where the oesophagus comes through the diaphragm.As it was impossible to apply a suture in that situation I determined to pack with iodoform gauze for thirty-six hours, and recovery was uninterrupted, and three years after- wards she was in perfect health.
Simultaneous left and right ventricular contractile dysfunction induced by right coronary ischaemia is partly relieved by pericardiectomy
Authors: C.I. Brookes, P.A. White, H.B. Ravn, U. Moeldrup, H. Soerensen, P.J. Oldershaw, A.N. Redington
Journal: Journal of the American College of Cardiology (1998)
MDSC and TGFβ Are Required for Facilitation of Tumor Growth in the Lungs of Mice Exposed to Carbon Nanotubes
Authors: Anna A. Shvedova, Elena R. Kisin, Naveena Yanamala, Alexey V. Tkach, Dmitriy W. Gutkin, Alexander Star, Galina V. Shurin, Valerian E. Kagan, Michael R. Shurin
Journal: Cancer Research (2015)

Abstract During the last decades, changes have been observed in the frequency of different histologic subtypes of lung cancer, one of the most common causes of morbidity and mortality, with a declining proportion of squamous cell carcinomas and an increasing proportion of adenocarcinomas, particularly in developed countries. This suggests the emergence of new etiologic factors and mechanisms, including those defining the lung microenvironment, promoting tumor growth. Assuming that the lung is the main portal of entry for broadly used nanomaterials and their established proinflammatory propensities, we hypothesized that nanomaterials may contribute to changes facilitating tumor growth. Here, we report that an acute exposure to single-walled carbon nanotubes (SWCNT) induces recruitment and accumulation of lung-associated myeloid-derived suppressor cells (MDSC) and MDSC-derived production of TGFβ, resulting in upregulated tumor burden in the lung. The production of TGFβ by MDSC requires their interaction with both SWCNT and tumor cells. We conclude that pulmonary exposure to SWCNT favors the formation of a niche that supports ingrowth of lung carcinoma in vivo via activation of TGFβ production by SWCNT-attracted and -presensitized MDSC. Cancer Res; 75(8); 1615–23. ©2015 AACR.
A Heuristic Proposal for Understanding Steroidogenic Processes
Authors: SEYMOUR LIEBERMAN, NORMA J. GREENFIELD, ADELE WOLFSON
Journal: Endocrine Reviews (1984)

The generally accepted pathways of steroidogenesis are customarily presented by a scheme such as that shown in Fig. 1. This two-dimensional picture can be conveniently reproduced on a printed page and is easily memorized. It provides, however, too simplistic a view which can lead to serious misconceptions. By depicting the biochemical transformations it concentrates on the apparent common features of the various pathways but ignores many important differences. The scheme indicates that one sterol, cholesterol, serves as a precursor for all the hormones. The possibility that other derivatives of cholesterol may also be progenitors of important steroidal products is not taken into account. Cholesterol esters, particularly cholesterol sulfate, are examples of such precursors. For more than 15 years (1) it has been known that the abundant adrenal secretory product, dehydroisoandrosterone sulfate, can be biosynthesized from cholesterol sulfate through pathways that involve sulfated intermediates which, it may be noted, do not appear in the scheme shown in Fig. 1. The scheme further assumes that the intermediates in the various processes are stable, isolatable compounds (such as pregnenolone, 17-hydroxypregnenolone,1etc.). However, decade-old evidence suggests that in at least some, if not all, processes the true intermediates are probably complexed with some components of the enzyme systems catalyzing the processes (2) and therefore the isolation of a stable entity from excreta or as a product of an in vitro experiment does not constitute proof of its intermediacy.
Bacillus Calmette-Guérin Osteomyelitis Mimicking Spinal Metastasis from Urothelial Cell Carcinoma of the Bladder
Authors: Amit R. Patel, Edmund S. Sabanegh, J. Stephen Jones, Steven M. Gordon, Mitchell Ballin, Paul M. Ruggieri, Andrew J. Stephenson
Journal: European Urology (2009)
Clindamycin for Acne
Authors: Ian R. Innes
Journal: JAMA (1976)

<h3>To the Editor.—</h3> In the light of current appreciation of the risk of severe and sometimes lethal acute colitis due to clindamycin, I hope that most physicians will disagree with the conclusion of Christian and Krueger that "clindamycin appears to be a valuable additional drug in the treatment of acne."<sup>1</sup>With their 13-week treatment, noticeable improvement occurred in just over twice as many clindamycin-treated patients as in those treated with placebo. Of the 44 patients given clindamycin, nine had diarrhea; in only one was this considered severe enough for the therapy to be stopped. The incidence of severe colitis, similar to pseudomembranous colitis, associated with clindamycin has not yet been determined, but its occurrence is well established (<i>JAMA</i>223:1379, 1973;<i>Lancet</i>1:451, 1974), and there is an increasing number of reported deaths. Manifestations of the condition may first appear two to three weeks after the end of clindamycin therapy.
Molecular identification of bacterial 16S ribosomal RNA gene in liver tissue of primary biliary cirrhosis: Is Propionibacterium acnes involved in granuloma formation?
Authors: Kenichi Harada, Koichi Tsuneyama, Yoshiko Sudo, Shinji Masuda, Yasuni Nakanuma
Journal: Hepatology (2001)

The etiopathogenesis of primary biliary cirrhosis (PBC) remains speculative. Epithelioid granulomas are often found in the vicinity of damaged interlobular bile ducts in PBC, raising the possibility of a reaction to microbial materials. In this study, we tried to detect and identify bacterial DNA within granulomatous lesions in PBC. Using liver sections from 9 patients with PBC and 13 control livers, granuloma in portal tracts, portal tracts without granuloma, and adjacent hepatic parenchyma were selectively microdissected from sections, and then DNA was extracted from them. First, part of the bacterial 16S ribosomal RNA (rRNA) gene was amplified from DNA samples extracted from 5 PBC and 6 control livers, and their amplicons were sequenced for the identification of bacterial species. Several indigenous bacteria were identified. Among them, Propionibacterium acnes (P. acnes) was detected as a major clone in 20% to 50% of sequenced clones from granuloma of PBC, but the detection rate of P. acnes was 0% to 20% in those cloned from adjacent hepatic parenchyma of PBC. Then, a P. acnes-specific PCR was performed using all microdissected samples. Distinct PCR products were identified in epithelioid granuloma in all 9 PBC cases. The result that P. acnes DNA is present as a major clone in granulomas of PBC, suggest that P. acnes is involved in the pathogenesis of granuloma in PBC.
Disorder of the long head of the biceps tendon
Authors: Benno Ejnisman, Gustavo Cará Monteiro, Carlos Vicente Andreoli, Alberto de Castro Pochini
Journal: British Journal of Sports Medicine (2010)

This paper focuses on biceps injuries in shoulder surgery. This topic is currently of great interest, and there has been much discussion about diagnosis, treatment and prevention. Biceps tendon pathology exists in many forms and is frequently associated with other shoulder disorders. These facts must be taken into consideration in the evaluation and treatment of patients with long head of the biceps pathology. There is much controversy about the long head of the biceps tendon (LHBT). The clinical significance to shoulder function, diagnosis and treatment are still a source of debate. The purpose of this review is to discuss the anatomy, function, pathology, clinical manifestation, physical examination, imaging and treatment of disorders of the LHBT.