tbuckley/cabot-search huggingface dataset:
<i>In vitro</i> Drug Sensitivity Predicts Response and Survival after Individualized Sensitivity-Directed Chemotherapy in Metastatic Melanoma: A Multicenter Phase II Trial of the Dermatologic Cooperative Oncology Group
Authors: Selma Ugurel, Dirk Schadendorf, Claudia Pföhler, Karsten Neuber, Adina Thoelke, Jens Ulrich, Axel Hauschild, Konstanze Spieth, Martin Kaatz, Werner Rittgen, Stefan Delorme, Wolfgang Tilgen, Uwe Reinhold
Journal: Clinical Cancer Research (2006)

In vitro sensitivity assays are promising tools to predict the individual outcome of different chemotherapy regimens. However, a direct association between in vitro and in vivo chemosensitivity has to be shown by clinical studies. This multicenter phase II trial was aimed to investigate the efficacy of a sensitivity-directed, first-line chemotherapy in metastasized melanoma patients, and to prove an association between in vitro sensitivity and therapy outcome.The primary study end point was objective response; secondary end points were safety, overall survival, and progression-free survival. Viable tumor cells obtained from metastatic lesions were tested for chemosensitivity to seven single drugs and five drug combinations using an ATP-based luminescence viability assay.Out of 82 recruited patients (intention-to-treat), 57 received assay-directed chemotherapy and 53 were evaluable for all study end points (per protocol). The drug combinations used were gemcitabine+treosulfan, paclitaxel+cisplatin, paclitaxel+doxorubicin, and gemcitabine+cisplatin. The per protocol population could be divided into 22 (42%) chemosensitive and 31 (58%) chemoresistant patients by an arbitrary chemosensitivity index. Objective response was 36.4% in chemosensitive patients compared with 16.1% in chemoresistant patients (P=0.114); progression arrest (complete response+partial response+stable disease) was 59.1% versus 22.6% (P=0.01). Chemosensitive patients showed an increased overall survival of 14.6 months compared with 7.4 months in chemoresistant patients (P=0.041).In vitro chemosensitivity testing may be worthy of further exploration to see if it could be a useful tool to predict the outcome of melanoma patients treated with a sensitivity-directed chemotherapy. Therefore, these preliminary results will be evaluated by a planned phase III trial using a randomized, standard-regimen controlled setting.
RICKETS: A THEORY OF THE METABOLIC DISTURBANCES AND OF ITS ASSOCIATION WITH TETANY
Authors: D. N. Paton
Journal: BMJ (1922)

Conclusion.The consideration of the evidence suggests that an error in the metabolism of lecitlhin, probably in the liver, may be a causal factor in the failure of bone formation in rickets, and that this faulty metabolism may in some cases be accom- panied by an increased conversion of cliolin into guanidin compounds, thus explain-ing the association of tetany with rickets.Tihe theory is put forward tentatively in the lhope that it may indicate lines for further work upon the nature of the disturbance in rickets.
Prevalence of symptoms of asthma, rhinitis and eczema in 13‐ to 14‐year‐old children in Africa: the International Study of Asthma and Allergies in Childhood Phase III
Authors: N. Ait‐Khaled, J. Odhiambo, N. Pearce, K. S. Adjoh, I. A. Maesano, B. Benhabyles, Z. Bouhayad, E. Bahati, L. Camara, C. Catteau, A. El Sony, F. O. Esamai, I. E. Hypolite, K. Melaku, O. A. Musa, L. Ng'ang'a, B. O. Onadeko, O. Saad, M. Jerray, J. M. Kayembe, N. B. Koffi, F. Khaldi, C. Kuaban, K. Voyi, J. M'Boussa, O. Sow, O. Tidjani, H. J. Zar
Journal: Allergy (2007)

Phase I of the International Study of Asthma and Allergies in Childhood has provided valuable information regarding international prevalence patterns and potential risk factors in the development of asthma, allergic rhinoconjunctivitis and eczema. However, in Phase I, only six African countries were involved (Algeria, Tunisia, Morocco, Kenya, South Africa and Ethiopia). Phase III, conducted 5–6 years later, enrolled 22 centres in 16 countries including the majority of the centres involved in Phase I and new centres in Morocco, Tunisia, Democratic Republic of Congo, Togo, Sudan, Cameroon, Gabon, Reunion Island and South Africa. There were considerable variations between the various centres of Africa in the prevalence of the main symptoms of the three conditions: wheeze (4.0–21.5%), allergic rhinoconjunctivitis (7.2–27.3%) and eczema (4.7–23.0%). There was a large variation both between countries and between centres in the same country. Several centres, including Cape Town (20.3%), Polokwane (18.0%), Reunion Island (21.5%), Brazzaville (19.9%), Nairobi (18.0%), Urban Ivory Coast (19.3%) and Conakry (18.6%) showed relatively high asthma symptom prevalences, similar to those in western Europe. There were also a number of centres showing high symptom prevalences for allergic rhinoconjunctivitis (Cape Town, Reunion Island, Brazzaville, Eldoret, Urban Ivory Coast, Conakry, Casablanca, Wilays of Algiers, Sousse and Eldoret) and eczema (Brazzaville, Eldoret, Addis Ababa, Urban Ivory Coast, Conakry, Marrakech and Casablanca).
Validity of Adjuvant! Online program in older patients with breast cancer: a population-based study
Authors: Nienke A de Glas, Willemien van de Water, Ellen G Engelhardt, Esther Bastiaannet, Anton J M de Craen, Judith R Kroep, Hein Putter, Anne M Stiggelbout, Nir I Weijl, Cornelis J H van de Velde, Johanneke E A Portielje, Gerrit-Jan Liefers
Journal: The Lancet Oncology (2014)
Peptide-based ELISAs are not sensitive and specific enough to detect muscarinic receptor type 3 autoantibodies in serum from patients with Sjogren's syndrome
Authors: N. Roescher, A. Kingman, Y. Shirota, J. A. Chiorini, G. G. Illei
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> The detection of autoantibodies to the muscarinic receptor type 3 (M3R) in the serum of patients with Sjögrens syndrome (SS) by ELISA is controversial. A study was undertaken to test whether modification of M3R peptides could enhance the antigenicity and increase the detection of specific antibodies using an ELISA. <h3>Methods</h3> A series of controlled ELISAs was performed with serum from 71 patients with SS and 37 healthy volunteers (HV) on linear, citrullinated and/or cyclised and multi-antigenic peptides (MAP) of the three extracellular M3R loops to detect specific binding. <h3>Results</h3> Significant differences (p&lt;0.05) in optical density (OD) between serum from patients and HV were detected for a cyclised loop 1-derived peptide and the negative control peptide. Furthermore, there were no statistically significant differences between the frequency of positive patients (defined as OD &gt;2SDs above the mean of the HV) and HV on any of the peptides tested. <h3>Conclusions</h3> Binding of serum from patients with SS to M3R-derived peptides does not differ from binding to a control peptide in an ELISA and no significant binding to M3R-derived peptides was found in the serum from individual patients compared with HV. These data suggest that peptide-based ELISAs are not sufficiently sensitive and/or specific to detect anti-MR3 autoantibodies.
The Arg753Gln polymorphism of the human Toll-like receptor 2 gene in tuberculosis disease
Authors: A.C. Ogus, B. Yoldas, T. Ozdemir, A. Uguz, S. Olcen, I. Keser, M. Coskun, A. Cilli, O. Yegin
Journal: European Respiratory Journal (2004)

Toll-like receptor 2 (TLR2), a member of the Toll-like receptor family, plays an important role in recognition of, and subsequent immune response activation against, mycobacteria. The genetic polymorphism of TLR2 (arginine to glutamine substitution at residue 753 (Arg753Gln)) has been associated with a negative influence on TLR2 function, which may, in turn, determine the innate host response to mycobacteria. The aim of the present study was to investigate the Arg753Gln single nucleotide polymorphism of the TLR2 gene in tuberculosis (TB) patients compared to healthy controls. A retrospective case/control study was carried out. The Arg753Gln polymorphism of the TLR2 gene was studied in 151 TB patients compared to 116 ethnically and age-matched healthy control subjects. The TLR2 polymorphism (adenine (A) allele) was observed in 17.9 and 7.7% of TB patients and controls, respectively. When the ratios of the three genotypes were compared between the two groups, the AA genotype was found to be more significantly associated with TB. Allele frequencies for guanine (G) and A were found to be 0.95 and 0.05 in the control group and 0.86 and 0.14 in the TB patient group, respectively. The risk of developing TB disease was increased 6.04- and 1.60-fold for carriers of the AA and GA genotypes, respectively. In conclusion, the present data suggest that the arginine to glutamine substitution at residue 753 polymorphism of the Toll-like receptor 2 gene influences the risk of developing tuberculosis.
Role of occult blood loss in anaemia after partial gastrectomy
Authors: I. M. Baird, D. J. B. St. John, S. S. Nasser
Journal: Gut (1970)

The present investigation is a study of occult gastrointestinal blood loss in 20 anaemic postgastrectomy patients and 14 control subjects. One patient in the postgastrectomy group was found to be bleeding from undetected haemorrhoids. One patient in each group showed sensitivity to aspirin with greatly increased occult blood loss. The mean blood loss in 18 postgastrectomy patients with unexplained anaemia was 0.6 ± 0.5 ml/day compared with 0.5 ± 0.5 ml/day in 13 control subjects. Only two of the 19 anaemic postgastrectomy patients studied lost more than 2 ml blood/day. Aspirin blood loss in 18 postgastrectomy patients was 2.4 ± 2.1 ml/day, compared with 2.6 ± 2.7 ml/day in 13 controls. The pattern of aspirin blood loss is identical in both groups. All gastric biopsies obtained from nine patients with Polya gastrectomies showed changes of gastritis; some showed complete gastric atrophy and intestinal metaplasia. Occult gastrointestinal bleeding is not an important factor in the pathogenesis of anaemia after partial gastrectomy unless there is either stomal ulceration or a lesion completely unrelated to the partial gastrectomy. If occult bleeding is present after partial gastrectomy a careful search for the site of bleeding is indicated. Excessive intake of aspirin or increased sensitivity to aspirin was not shown to be a significant factor in the pathogenesis of the anaemia in this group of patients. However, because of the inability to augment iron absorption to compensate for blood loss, it would be inadvisable for the patient with a partial gastrectomy to take a high dosage of aspirin for long periods of time, unless aspirin-induced blood loss is measured and shown to be very low. Aspirin administered in low dosage is not contraindicated after partial gastrectomy.
Vulnerable Atherosclerotic Plaque Morphology in Apolipoprotein E–Deficient Mice Unable to Make Ascorbic Acid
Authors: Yukiko Nakata, Nobuyo Maeda
Journal: Circulation (2002)

Background— Oxidative stress is thought to play an important role in atherogenesis, suggesting that antioxidants could prevent coronary artery disease. However, the efficacy of vitamin C in reducing atherosclerosis is debatable in humans and has not been tested rigorously in animals. Methods and Results— Gulo −/− Apoe −/− mice were used to test a hypothesis that chronic vitamin C deficiency enhances the initiation and development of atherosclerosis. These mice are dependent on dietary vitamin C because of the lack of L-gulonolactone-γ-oxidase and are prone to develop atherosclerosis because of lacking apolipoprotein E. Beginning at 6 weeks of age, the Gulo −/− Apoe −/− mice were fed regular chow or Western-type diets containing high fat and supplemented with either 0.033 g or 3.3 g/L of vitamin C in their drinking water. This regimen produced mice with chronically low vitamin C (average 1.5 μg/mL in plasma) or high vitamin C (average 10 to 30 μg/mL in plasma). Morphometric analysis showed that within each sex, age, and diet group, the sizes of the atherosclerotic plaques were not different between low vitamin C mice and high vitamin C mice. However, advanced plaques in the low vitamin C mice had significantly reduced amounts of Sirius red–staining collagen (36.4±2.2% versus 54.8±2.3%, P &lt;0.0001), larger necrotic cores within the plaques, and reduced fibroproliferation and neovascularization in the aortic adventitia. Conclusions— Chronic vitamin C deficiency does not influence the initiation or progression of atherosclerotic plaques but severely compromises collagen deposition and induces a type of plaque morphology that is potentially vulnerable to rupture.
Cornish out of hours service still has staff shortages, CQC finds
Authors: A. O'Dowd
Journal: BMJ (2013)

An out of hours GP service run by the private company Serco has been criticised again in a new report for failing to provide enough staff to meet demand and forcing employees to work long hours.

Serco said, however, that many improvements had been made to the service in recent months, including recruitment of more GPs.

The main regulator of the NHS, the Care Quality Commission, has investigated the Cudmore House out of hours GP service, which is based in Truro, Cornwall, and found ongoing problems despite previous inspections that called for remedial action.1

Serco provides the service for the Cornwall and Isles …
Identification and Analysis of <i>In Vivo</i> VEGF Downstream Markers Link VEGF Pathway Activity with Efficacy of Anti-VEGF Therapies
Authors: Matthew J. Brauer, Guanglei Zhuang, Maike Schmidt, Jenny Yao, Xiumin Wu, Joshua S. Kaminker, Stefanie S. Jurinka, Ganesh Kolumam, Alicia S. Chung, Adrian Jubb, Zora Modrusan, Tomoko Ozawa, C. David James, Heidi Phillips, Benjamin Haley, Rachel N.W. Tam, Anne C. Clermont, Jason H. Cheng, Sherry X. Yang, Sandra M. Swain, Daniel Chen, Stefan J. Scherer, Hartmut Koeppen, Ru-Fang Yeh, Peng Yue, Jean-Philippe Stephan, Priti Hegde, Napoleone Ferrara, Mallika Singh, Carlos Bais
Journal: Clinical Cancer Research (2013)

The aim of this study was to identify conserved pharmacodynamic and potential predictive biomarkers of response to anti-VEGF therapy using gene expression profiling in preclinical tumor models and in patients.Surrogate markers of VEGF inhibition [VEGF-dependent genes or VEGF-dependent vasculature (VDV)] were identified by profiling gene expression changes induced in response to VEGF blockade in preclinical tumor models and in human biopsies from patients treated with anti-VEGF monoclonal antibodies. The potential value of VDV genes as candidate predictive biomarkers was tested by correlating high or low VDV gene expression levels in pretreatment clinical samples with the subsequent clinical efficacy of bevacizumab (anti-VEGF)-containing therapy.We show that VDV genes, including direct and more distal VEGF downstream endothelial targets, enable detection of VEGF signaling inhibition in mouse tumor models and human tumor biopsies. Retrospective analyses of clinical trial data indicate that patients with higher VDV expression in pretreatment tumor samples exhibited improved clinical outcome when treated with bevacizumab-containing therapies.In this work, we identified surrogate markers (VDV genes) for in vivo VEGF signaling in tumors and showed clinical data supporting a correlation between pretreatment VEGF bioactivity and the subsequent efficacy of anti-VEGF therapy. We propose that VDV genes are candidate biomarkers with the potential to aid the selection of novel indications as well as patients likely to respond to anti-VEGF therapy. The data presented here define a diagnostic biomarker hypothesis based on translational research that warrants further evaluation in additional retrospective and prospective trials.
<i>MDM2</i> Polymorphism, Survival, and Histology in Early-Stage Non–Small-Cell Lung Cancer
Authors: Rebecca Suk Heist, Wei Zhou, Lucian R. Chirieac, Thea Cogan-Drew, Geoffrey Liu, Li Su, Donna Neuberg, Thomas J. Lynch, John C. Wain, David C. Christiani
Journal: Journal of Clinical Oncology (2007)

Purpose MDM2 is a negative regulator of p53. The MDM2 309T/G polymorphism has been associated with differential MDM2 expression levels and inhibition of the p53 pathway. We hypothesized that the MDM2 G/G genotype may be associated with worse survival outcomes in lung cancer, especially in squamous cell cancers where p53 abnormalities are more common. Patients and Methods We evaluated the relationship between MDM2 polymorphism status and overall survival (OS) among patients with early-stage non–small-cell lung cancer (NSCLC) treated with surgical resection at Massachusetts General Hospital from 1992 to 2000. Kaplan-Meier methods and the log-rank test were used to compare survival by polymorphism status. Cox proportional hazards models were used to adjust for possible confounding variables. Results There were 383 patients in the analysis. In the early-stage population as a whole, the G/G genotype seemed to be associated with worse OS on adjusted analysis (adjusted hazard ratio = 1.57; 95% CI, 1.03 to 2.40; P = .04). Among patients with squamous histology, OS was significantly worse among those with the G/G genotype (P = .0001 by log-rank test), with 5-year survival rates among the genotypes of 59% for T/T, 53% for T/G, and 7% for G/G. Conclusion Our findings suggest that the G/G genotype of the MDM2 polymorphism is associated with worse OS among early-stage NSCLC patients, particularly those with squamous cell histology.
Monocytes and polymorphonuclear neutrophils of patients with streptococcal pharyngitis express increased numbers of type I IgG Fc receptors.
Authors: P M Guyre, A S Campbell, W D Kniffin, M W Fanger
Journal: Journal of Clinical Investigation (1990)

Studies using cultured cells have shown that gamma interferon (IFN-gamma) induces the expression of Fc gamma RI (the type I Fc receptor for IgG) on human polymorphonuclear neutrophils (PMN) and greatly increases the number of these receptors on human monocytes. Administration of rIFN-gamma in vivo also causes enhanced Fc gamma RI expression on these cell populations. Because streptococcal antigens are potent inducers of IFN-gamma in vitro, we postulated that IFN-gamma would be produced endogenously in vivo in patients with streptococcal infections. Such production of IFN-gamma in vivo, even at low levels, might be expected to induce the expression of Fc gamma RI on monocytes and neutrophils. To evaluate this possibility, we used monoclonal antibody 32 (mAb 32), which is specific for Fc gamma RI, to quantitate the expression of this receptor on human peripheral blood cells. We measured the binding of mAb 32 to monocytes and PMNs isolated from healthy donors and from patients with group A beta-hemolytic streptococcal (GABHS) pharyngitis. PMNs from healthy donors (n = 12) had 700 +/- 600 (mean +/- SD) mAb 32 binding sites. Patients with pharyngitis and negative throat culture for GABHS (n = 11) had 2,100 +/- 1,600 sites on their PMNs. In contrast, the PMNs from patients with documented GABHS pharyngitis (n = 12) had 11,600 +/- 7,500 mAb 32 binding sites on their surface. There was a similar change in the expression of Fc gamma RI on monocytes, with control monocytes having a mean of 19,900 +/- 3,200 mAb 32 binding sites per cell and the GABHS-positive monocytes having 47,500 +/- 21,400 sites. The GABHS-negative throat culture group had a slightly elevated number of Fc gamma RI with a mean of 28,200 +/- 8,400 sites. 10 patients with documented urinary tract infections and three patients with uncomplicated pyelonephritis had no elevation in Fc gamma RI expression. These studies demonstrate that a localized group A streptococcal infection can cause systemic activation of the entire circulating pool of phagocytes, and suggest that a similar level of activation is uncommon in localized gram-negative infections of the urinary tract.
Dexamethasone and The Long Acting β2-Adrenergic Receptor Agonist, R,R-formoterrol (RF), Upregulate CCAAT Enhancer Binding Protein (C/EBP) Gene Expression and Induce Production of The Immunoprotective Surfactant Protein D (SP-D) in Alveolar Epithelial Cells
Authors: K KRYTSKA, J DUNKELBERGER, E TONG, S KIERSTEIN, A HACZKU
Journal: Journal of Allergy and Clinical Immunology (2008)
Epididymitis in Prepuberal Boys
Authors: Arjan D. Amar
Journal: JAMA (1969)

Acute epididymitis in prepuberal boys is rare; when it does occur, it may be the first manifestation of urologic anomaly or disease. After the diagnosis of epididymitis is established, urologic investigation is essential. In the three boys described here, epididymitis heralded vesicoureteral reflux, which in turn was associated with major abnormalities of the urinary tract.
Multipoint determination of pressure-volume curves in human intervertebral discs.
Authors: H S Ranu
Journal: Annals of the Rheumatic Diseases (1993)

To gain further insight into the biomechanics of the human intervertebral disc and to determine a potential mechanism for causation and relief of symptoms related to a herniated disc, the pressure-volume relation was determined within the nucleus pulposus. Pressure was measured continuously within the nucleus pulposus in 17 intact lumbar discs from human cadavers by means of a miniature strain gauge at the tip of a size 4 French (1.3 mm) catheter inserted into the nucleus pulposus. The volume of the nucleus pulposus was increased at the slow, continuous rate of 0.034 ml/min by the pump regulated infusion of saline coloured with methylene blue. In 12 unloaded discs, nucleus pulposus pressure rose in a linear fashion (linear r = 0.96) from an initial mean pressure of 174 (SD 81) kPa. The mean rate of pressure rise was 327 (SD 109) kPa/ml volume increase. The peak pressure measured was 550 kPa; this was slightly higher than the capability of the transducer. Similar linear relations were obtained during infusion of saline into five vertically loaded discs fixed at the deformation produced by a 9.1 kg weight. The data define the pressure-volume relation within the disc and show that the nucleus pulposus, surrounded by the relatively inelastic annulus and the solid vertebral end plates, has the properties of a tight hydraulic space in which a large pressure rise will regularly result from a small increase in volume. Presumably the opposite is also true. The data may provide a biomechanical basis for the physiological variation in symptoms related to the disc, and for any benefits obtained from interventions designed to remove disc tissue.
Is the Pregnancy Hormone Relaxin Also a Vasodilator Peptide Secreted by the Heart?
Authors: Carol Fisher, Margaret MacLean, Ian Morecroft, Alison Seed, Fiona Johnston, Christopher Hillier, John McMurray
Journal: Circulation (2002)

Background — It has been shown recently that the pregnancy and parturition hormone, relaxin, is secreted by the heart. This study examined the effects of relaxin in small human resistance arteries from the systemic and pulmonary circulations. Methods and Results — Arteries were obtained from gluteal biopsies and resected lung tissue and studied with the use of wire myography. Cumulative concentration relaxation curves were constructed in systemic arteries with substance P, epoprostenol, atrial natriuretic peptide, and relaxin (concentration range 10 −13 -10 −7 M). The maximal responses were 88(±5)%, 67(±10)%, 52(±16)% and 66(±16)%, respectively. Endothelium removal virtually abolished the action of relaxin. Relaxin had no vasodilator effect in pulmonary arteries. Conclusions — Relaxin is a powerful dilator of systemic resistance arteries secreted by the heart that may contribute to cardiovascular regulation.