tbuckley/cabot-search huggingface dataset:
Incidence of schizophrenia in ethnic minorities in London: ecological study into interactions with environment
Authors: J Boydell, J van Os, K McKenzie, J Allardyce, R Goel, R G McCreadie, R M Murray
Journal: BMJ (2001)

To determine whether the incidence of schizophrenia among people from non-white ethnic minorities is greater in neighbourhoods where they constitute a smaller proportion of the total population.Ecological design including retrospective study of case records to calculate the incidence of schizophrenia in the ethnic minority population across electoral wards and multi-level analysis to examine interaction between individuals and environment.15 electoral wards in Camberwell, South London.All people aged 16 years and over who had contact with psychiatric services during 1988-97.Incidence rates of schizophrenia according to Research Diagnostic Criteria.The incidence of schizophrenia in non-white ethnic minorities increased significantly as the proportion of such minorities in the local population fell. The incidence rate ratio varied in a dose-response fashion from 2.38 (95% confidence interval 1.49 to 3.79) in the third of wards where non-white ethnic minorities formed the largest proportion (28-57%) of the local population to 4.4 (2.49 to 7.75) in the third of wards where they formed the smallest proportion (8-22%).The incidence of schizophrenia in non-white ethnic minorities in London is greater when they comprise a smaller proportion of the local population.
Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen.
Authors: R J Robb, W C Greene, C M Rusk
Journal: The Journal of Experimental Medicine (1984)

Interleukin 2 promotes proliferation of T cells by virtue of its interaction with a high-affinity cell surface receptor. This receptor is a 55,000 mol wt glycoprotein that is also recognized by the murine monoclonal antibody, anti-Tac. Quantitative binding studies with radiolabeled IL-2 and anti-Tac, however, initially indicated far more antibody binding sites per cell than IL-2 binding sites. Extension of the IL-2 binding analysis to concentrations several thousand-fold higher than that necessary for the T cell proliferative response demonstrated the existence of a class (or classes) of low-affinity IL-2 binding sites. Inclusion of the low-affinity IL-2 binding greatly reduced the quantitative discrepancy in the ligand binding assays. That the low-affinity binding, as well as the high-affinity interaction, was associated with the Tac molecule was indicated by the finding that the antibody could substantially or totally block the entire spectrum of IL-2 binding and by the finding that IL-2 could in turn block all radiolabeled anti-Tac binding. The low-affinity sites were found on activated T cells, several human and murine T cell lines and two examples of Tac-positive B cells. The physiological role of the low-affinity IL-2 binding sites and the molecular changes in the Tac protein that give rise to the affinity differences remain open to investigation.
A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer.
Authors: Philip M Arlen, James L Gulley, Catherine Parker, Lisa Skarupa, Mary Pazdur, Dennis Panicali, Patricia Beetham, Kwong Y Tsang, Douglas W Grosenbach, Jarett Feldman, Seth M Steinberg, Elizabeth Jones, Clara Chen, Jennifer Marte, Jeffrey Schlom, William Dahut
Journal: Clinical Cancer Research (2006)

Abstract PURPOSE: Docetaxel has activity against androgen-independent prostate cancer and preclinical studies have shown that taxane-based chemotherapy can enhance antitumor response of vaccines. The primary objective of this study was to determine if concurrent docetaxel (with dexamethasone) had any effect on generating an immune response to the vaccine. Secondary end points were whether vaccine could be given safely with docetaxel and the clinical outcome of the treatment regimen. EXPERIMENTAL DESIGN: The vaccination regimen was composed of (a) recombinant vaccinia virus (rV) that expresses the prostate-specific antigen gene (rV-PSA) admixed with (b) rV that expresses the B7.1 costimulatory gene (rV-B7.1), and (c) sequential booster vaccinations with recombinant fowlpox virus (rF-) containing the PSA gene (rF-PSA). Patients received granulocyte macrophage colony-stimulating factor with each vaccination. Twenty-eight patients with metastatic androgen-independent prostate cancer were randomized to receive either vaccine and weekly docetaxel or vaccine alone. Patients on the vaccine alone arm were allowed to cross over to receive docetaxel alone at time of disease progression. The ELISPOT assay was used to monitor immune responses for PSA-specific T cells. RESULTS: The median increase in these T-cell precursors to PSA was 3.33-fold in both arms following 3 months of therapy. In addition, immune responses to other prostate cancer-associated tumor antigens were also detected postvaccination. Eleven patients who progressed on vaccine alone crossed over to receive docetaxel at time of progression. Median progression-free survival on docetaxel was 6.1 months after receiving vaccine compared with 3.7 months with the same regimen in a historical control. CONCLUSION: This is the first clinical trial to show that docetaxel can be administered safely with immunotherapy without inhibiting vaccine specific T-cell responses. Furthermore, patients previously vaccinated with an anticancer vaccine may respond longer to docetaxel compared with a historical control of patients receiving docetaxel alone. Larger prospective clinical studies will be required to validate these findings.
Influence of body mass index on the response to asthma controller agents
Authors: M. Peters-Golden
Journal: European Respiratory Journal (2006)

The incidence of asthma has been positively associated with obesity. Asthma comprises diverse "phenotypes" reflecting heterogeneity in a number of characteristics, including response to therapy. The present authors examined whether body mass index (BMI) influenced the response to placebo, as well as to two asthma controller medications. A post hoc analysis was performed, pooling data from four double-blind, placebo-controlled studies randomising 3,073 moderate asthmatic adults to montelukast (n=1,439), beclomethasone (n=894) or placebo (n=740). The primary end point was asthma control days; other end points were forced expiratory volume in one second, beta-agonist use and nocturnal awakening. Analyses were conducted using BMI classification into normal (<25.0 kg.m-2; 52% of patients), overweight (25-29.9 kg.m-2; 32%) and obese (>or=30.0 kg.m-2; 16%) categories, as well as BMI as a continuous variable. The treatment groups were balanced for BMI, demographic characteristics and parameters of asthma control. The placebo response for all end points was generally lower with increasing BMI. Similarly, the response to the inhaled corticosteroid decreased, whereas the response to the leukotriene antagonist remained stable. In conclusion, post hoc data from the present study suggested that body mass index may influence the natural history of asthma control (as reflected by response to placebo) and may differentially influence response to the two active agents, warranting explicit testing in future prospective studies.
Superantigenicity of streptococcal M protein.
Authors: M Tomai, M Kotb, G Majumdar, E H Beachey
Journal: The Journal of Experimental Medicine (1990)

M proteins that define the serotypes of group A streptococci are powerful blastogens for human T lymphocytes. The mechanism by which they activate T cells was investigated and compared with the conventional T cell mitogen phytohemagglutinin, and the known superantigen staphylococcal enterotoxin B. Although major histocompatibility complex (MHC) class II molecules are required for presentation, there is no MHC restriction, since allogeneic class II molecules presented the bacterial protein to human T cells. Type 5 M protein appears to bind class II molecules on the antigen-presenting cells and stimulate T cells bearing V beta 8 sequences. Our results indicate that this streptococcal M protein is a superantigen and suggest a possible mechanism of its role in the pathogenesis of the postinfectious autoimmune sequelae.
The Osteocyte: An Endocrine Cell … and More
Authors: Sarah L. Dallas, Matthew Prideaux, Lynda F. Bonewald
Journal: Endocrine Reviews (2013)

Few investigators think of bone as an endocrine gland, even after the discovery that osteocytes produce circulating fibroblast growth factor 23 that targets the kidney and potentially other organs. In fact, until the last few years, osteocytes were perceived by many as passive, metabolically inactive cells. However, exciting recent discoveries have shown that osteocytes encased within mineralized bone matrix are actually multifunctional cells with many key regulatory roles in bone and mineral homeostasis. In addition to serving as endocrine cells and regulators of phosphate homeostasis, these cells control bone remodeling through regulation of both osteoclasts and osteoblasts, are mechanosensory cells that coordinate adaptive responses of the skeleton to mechanical loading, and also serve as a manager of the bone's reservoir of calcium. Osteocytes must survive for decades within the bone matrix, making them one of the longest lived cells in the body. Viability and survival are therefore extremely important to ensure optimal function of the osteocyte network. As we continue to search for new therapeutics, in addition to the osteoclast and the osteoblast, the osteocyte should be considered in new strategies to prevent and treat bone disease.
Transgenic mice overexpressing human KvLQT1 dominant-negative isoform Part I: Phenotypic characterisation
Authors: S Demolombe
Journal: Cardiovascular Research (2001)

Objectives: The KCNQ1 gene encodes the KvLQT1 potassium channel, which generates in the human heart the slow component of the cardiac delayed rectifier current, IKs. Mutations in KCNQ1 are the most frequent cause of the congenital long QT syndrome. We have previously cloned a cardiac KCNQ1 human isoform, which exerts a strong dominant-negative effect on KvLQT1 channels. We took advantage of this dominant-negative isoform to engineer an in vivo model of KvLQT1 disruption, obtained by overexpressing the dominant-negative subunit under the control of the α-myosin heavy chain promoter. Results: Three different transgenic lines demonstrated a phenotype with increasing severity. Functional suppression of KvLQT1 in transgenic mice led to a markedly prolonged QT interval associated with sinus node dysfunction. Transgenic mice also demonstrated atrio-ventricular block leading to occasional Wenckebach phenomenon. The atrio-ventricular block was associated with prolonged AH but normal HV interval in His recordings. Prolonged QT interval correlated with prolonged action potential duration and with reduced K+ current density in patch-clamp experiments. RNase protection assay revealed remodeling of K+ channel expression in transgenic mice. Conclusions: Our transgenic mouse model suggests a role for KvLQT1 channels not only in the mouse cardiac repolarisation but also in the sinus node automaticity and in the propagation of the impulse through the AV node.
Sildenafil Inhibits Altitude-induced Hypoxemia and Pulmonary Hypertension
Authors: Jean-Paul Richalet, Pierre Gratadour, Paul Robach, Isabelle Pham, Michèle Déchaux, Aude Joncquiert-Latarjet, Pascal Mollard, Julien Brugniaux, Jérémy Cornolo
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Exposure to high altitude induces pulmonary hypertension that may lead to life-threatening conditions. In a randomized, double-blind, placebo-controlled study, the effects of oral sildenafil on altitude-induced pulmonary hypertension and gas exchange in normal subjects were examined. Twelve subjects (sildenafil [SIL] n = 6; placebo [PLA] n = 6) were exposed for 6 days at 4,350 m. Treatment (3 x 40 mg/day) was started 6 to 8 hours after arrival from sea level to high altitude and maintained for 6 days. Systolic pulmonary artery pressure (echocardiography) increased at high altitude before treatment (+29% versus sea level, p < 0.01), then normalized in SIL (-6% versus sea level, NS) and remained elevated in PLA (+21% versus sea level, p < 0.05). Pulmonary acceleration time decreased by 27% in PLA versus 6% in SIL (p < 0.01). Cardiac output and systemic blood pressures increased at high altitude then decreased similarly in both groups. Pa(O(2)) was higher and alveolar-arterial difference in O(2) lower in SIL than in PLA at rest and exercise (p < 0.05). The altitude-induced decrease in maximal O(2) consumption was smaller in SIL than in PLA (p < 0.05). Sildenafil protects against the development of altitude-induced pulmonary hypertension and improves gas exchange, limiting the altitude-induced hypoxemia and decrease in exercise performance.
Inquiry into the Modus Operandi of Therapeutic Agents
Authors: R. H. Powell
Journal: BMJ (1852)

Under circumstances of emergen.cythey might, like the meat biseuit and the extracts of meat, prove invaluakie; occupyg, if packed up in tin cases, a very small space, and admitting of being kept for an indefinite period.From the preceding considerations, the following practical conclu- sions in reference to the question before our naval and military authorities may be made.. ... 1.That in the supplies of troops and mariners, especially in time of war, black bread should be selected, as more nutritious, more wholesome, more easily procured than -w,hite bread.2. That as an aliment biscuit is superior to either, and as such might be more often employed.3. That if possible, the bread and biscuit should be made with upper-malt dough and flour, as being then more nutritious.4. That preserved meats, similar to thope introduced by Mr. Gold- ner, should continue to be issued i care only being taken to ensure their careful preparation, if necessary, under Government control, and mean adopted to prevent their being carelessly stowed away in damp places.5. That measures should be adopted to encourage the manufacture of meat biscuit, extracts of meat, for field and hospital service, and for provisioning fortresses, especiWly in time of war.6.That in the supplies served out to the navy, especially in addi- tion those enumerated above, it wou1,,e_well to conjoin prepared extracts of blood, milk, coffee, tea, cocoa, etc., and preserved vege- tables for more general use.19, Dorset Square, May 1852.
Phase II Trial of Carcinoembryonic Antigen Radioimmunotherapy With <sup>131</sup>I-Labetuzumab After Salvage Resection of Colorectal Metastases in the Liver: Five-Year Safety and Efficacy Results
Authors: Torsten Liersch, Johannes Meller, Bettina Kulle, Thomas M. Behr, Peter Markus, Claus Langer, B. Michael Ghadimi, William A. Wegener, Jacqueline Kovacs, Ivan D. Horak, Heinz Becker, David M. Goldenberg
Journal: Journal of Clinical Oncology (2005)

Although complete resection (R0) of liver metastases (LM) remains the treatment of choice for colorectal cancer (CRC) patients amenable to curative therapy, only approximately one third survive for 5 years. The objective of this phase II study was to evaluate the safety and efficacy of radioimmunotherapy (RAIT) after salvage resection of LM.Twenty-three patients who underwent surgery for LM of CRC received a dose of 40 to 60 mCi/m2 of 131I-labetuzumab, which is a humanized monoclonal antibody against carcinoembryonic antigen. Safety (n = 23), disease-free survival (DFS; n = 19), and overall survival (OS; n = 19) were determined.With a median follow-up of 64 months, the median OS time from the first liver resection for RAIT patients was 68.0 months (95% CI, 46.0 months to infinity), and the median DFS time was 18.0 months (95% CI, 11.0 to 31.0 months). The 5-year survival rate was 51.3%. RAIT benefited patients independently of bilobar involvement, size and number of LM, and resection margins. The major adverse effect was transient myelosuppression, resulting mostly in grade < or = 3 neutropenia and/or thrombocytopenia.Because both the median OS and 5-year survival rates seem to be improved with adjuvant RAIT after complete LM resection in CRC, compared with historical and contemporaneous controls not receiving RAIT, these results justify further evaluation of this modality in a multicenter, randomized trial.
Is thiopurine therapy in ulcerative colitis as effective as in Crohn's disease?
Authors: S Ghosh
Journal: Gut (2005)

There is evidence in support of the use of azathioprine in steroid dependent ulcerative colitis patients, confirming the steroid sparing effect of azathioprine

The use of azathioprine or 6-mercaptopurine for maintaining remission in Crohn’s disease patients who are steroid dependent or resistant is unequivocally supported by evidence from randomised controlled clinical trials. The same, however, cannot be said for the use of immunomodulator therapy in ulcerative colitis (UC). Trials are scanty, small in size, conflicting in results, and clinical practice is dominated by support from low quality evidence from open series reports. In addition, outcome measures used in different trials vary considerably, and the tools used to assess clinical disease activity are numerous and diverse.

In the first randomised controlled trial, conducted way back in 1974 by Jewell and Truelove,1 a two by three stratification was used. Inpatients or outpatients with active UC were stratified into first attack, short history (less than five years), and long history (more than five years). The acute episode was treated with corticosteroids, either 20 mg oral prednisolone plus steroid enemas for outpatients or 40 mg prednisolone 21-phosphate with rectal hydrocortisone for inpatients. Azathioprine was added immediately at a dose of 2.5 mg/kg. In the first 40 patients, the azathioprine dose was reduced after three months to 1.5–2.0 mg/kg whereas in the next 40 patients the dose was maintained at 2.5 mg/kg throughout the trial period of one year. It was not surprising that azathioprine was of no value in induction of remission as the end point was at one month after commencement of azathioprine. As maintenance therapy, azathioprine lacked value in patients being treated for the first attack of UC. Although there was a trend towards some benefit in patients with established UC who had relapsed, this was not statistically significant. As the …
Mammographic Breast Density Response to Aromatase Inhibition
Authors: Celine M. Vachon, Vera J. Suman, Kathleen R. Brandt, Matthew L. Kosel, Aman U. Buzdar, Janet E. Olson, Fang-Fang Wu, Lynn M. Flickinger, Giske Ursin, Catherine R. Elliott, Lois Shepherd, Richard M. Weinshilboum, Paul E. Goss, James N. Ingle
Journal: Clinical Cancer Research (2013)

Mammographic breast density (MBD) is decreased by tamoxifen, but the effect of aromatase inhibitors is less clear.We enrolled early-stage postmenopausal patients with breast cancer initiating adjuvant aromatase inhibitor therapy and ascertained mammograms before and at an average 10 months of aromatase inhibitor therapy. We matched cases to healthy postmenopausal women (controls) from a large mammography screening cohort on age, baseline body mass index, baseline MBD, and interval between mammograms. We estimated change in MBD using a computer-assisted thresholding program (Cumulus) and compared differences between cases and matched controls.In predominantly White women (96%), we found 14% of the 387 eligible cases had a MBD reduction of at least 5% after an average of 10 months of aromatase inhibitor therapy. MBD reductions were associated with higher baseline MBD, aromatase inhibitor use for more than 12 months, and prior postmenopausal hormone use. Comparing each case with her matched control, there was no evidence of an association of change in MBD with aromatase inhibitor therapy [median case-control difference among 369 pairs was -0.1% (10th and 90th percentile: -5.9%, 5.2%) P = 0.51]. Case-control differences were similar by type of aromatase inhibitor (P's 0.41 and 0.56); prior use of postmenopausal hormones (P = 0.85); baseline MBD (P = 0.55); and length of aromatase inhibitor therapy (P = 0.08).In postmenopausal women treated with aromatase inhibitors, 14% of cases had a MBD reduction of more than 5%, but these decreases did not differ from matched controls. These data suggest that MBD is not a clinically useful biomarker for predicting the value of aromatase inhibitor therapy in White postmenopausal women.
From the authors: Uneven use of noninvasive ventilation in acute respiratory failure in Europe
Authors: C. Crimi, A. Noto, P. Princi, A. Esquinas, S. Nava
Journal: European Respiratory Journal (2011)

From the authors:

We are grateful to J. Nasilowski and colleagues for having pointed out the important problem of the use of noninvasive ventilation (NIV) in Eastern European countries. Unfortunately, we were unaware of the survey conducted in Poland [1], mentioned by the authors, simply because it was not found using any medical search engine ( i.e. Pubmed and similar).

We agree with J. Nasilowski and colleagues that the use of NIV may be different in some geographical locations. However, as stated in the Methods section of our study: “The survey was sent to all members of the Respiratory Intensive Care Assembly from the …
Acute Aortic Dissection Determines the Fate of Initially Untreated Aortic Segments in Marfan Syndrome
Authors: Florian S. Schoenhoff, Silvan Jungi, Martin Czerny, Eva Roost, David Reineke, Gabor Matyas, Beat Steinmann, Juerg Schmidli, Alexander Kadner, Thierry Carrel
Journal: Circulation (2013)

The aim of the current study was to investigate incidence and causes of surgical interventions in primarily nontreated aortic segments after previous aortic repair in patients with Marfan syndrome.Retrospective analysis of 86 consecutive Marfan syndrome patients fulfilling Ghent criteria that underwent 136 aortic surgeries and were followed at this institution in the past 15 years. Mean follow-up was 8.8±6.8 y. Thirty-day, 6-month, 1-year, and overall mortality was 3.5%, 5.8%, 7.0%, and 12.8%, respectively. Ninety-two percent of patients initially presented with aortic root, ascending aortic or arch lesions, whereas 8% presented with descending aortic or thoraco-abdominal lesions. Primary presentation was acute aortic dissection (AAD) in 36% (77% type A, 23% type B) and aneurismal disease in 64%. Secondary complete arch replacement had to be performed in only 6% of patients without AAD, but in 36% with AAD (P=0.0005). In patients without AAD, 11% required surgery on primarily nontreated aortic segments (5 of 6 patients experienced type B dissection during follow-up), whereas in patients after AAD, 48% underwent surgery of initially nontreated aortic segments (42% of patients with type A and 86% of those with type B dissection; P=0.0002).The need for surgery in primarily nontreated aortic segments is precipitated by an initial presentation with AAD. Early elective surgery is associated with low mortality and reintervention rates. Type B dissection in patients with Marfan syndrome is associated with a high need for extensive aortic repair, even if the dissection is being considered uncomplicated by conventional criteria.