tbuckley/cabot-search huggingface dataset:
Cetuximab in Advanced Bladder Cancer
Authors: Stéphane Culine
Journal: Journal of Clinical Oncology (2013)

TO THE EDITOR: Second-line treatment for patients with advanced bladder cancer who experience progression after first-line platinum-based regimens remains an unmet medical need. In recent years, vinflunine was the first agent to be approved by a regulatory agency (European Medicine Agency) in this setting. Wong et al 1 should be congratulated for having conducted a randomizedphaseIItrialofcetuximabwithorwithoutpaclitaxelin39 patients with previously treated urothelial cancer. The authors concluded that cetuximab has limited activity as a single agent, whereas the combination of cetuximab and paclitaxel warrants additional study. However, a few points concerning the design of this study could have altered the conclusions. Selection of Patients Wong et al 1 included patients experiencing failure during firstline chemotherapy for advanced disease or perioperative (neoadjuvant or adjuvant) therapy without any restriction on the time from previous treatment. Progression of disease within 6 months in the
UK community prevalence of knee chondrocalcinosis: evidence that correlation with osteoarthritis is through a shared association with osteophyte
Authors: R L Neame
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objectives:</b> (1) To estimate the prevalence of chondrocalcinosis (CC) in the community and to characterise its compartmental distribution within the knee. (2) To investigate the associations between CC and individual radiographic features of osteoarthritis (OA) at the tibiofemoral joint (TFJ) and patellofemoral joint (PFJ). <b>Methods:</b> From three community questionnaire studies investigating the prevalence of knee pain, standing anteroposterior and skyline radiographs were obtained on 1727 subjects (1084 women, 643 men; mean age 63.7; 999 (58%) with knee pain). A single observer recorded the presence and site of CC and graded osteophyte and joint space narrowing (JSN) using a line atlas. "OA" was globally defined as the presence of definite osteophyte and definite JSN. Minimum joint space width (JSW) was measured to 0.1 mm with a metred dial caliper <b>Results:</b> (1) The crude prevalence of CC was 7.0% (95% confidence interval (CI) 5.8 to 8.2). This showed a strong association with age. The age adjusted odds ratio (aOR) for CC in women <i>v</i> men was 0.79 (95% CI 0.52 to 1.12). The age, sex, and knee pain standardised estimate for those aged &gt;40 in Nottingham, UK was 4.5%. Patellofemoral CC was seen in only nine cases, all with tibiofemoral CC. (2) The age-sex aOR for the association between CC and OA was 2.08 at the PFJ (1.38 to 3.12) and 2.00 (1.11 to 3.60) at the TFJ. There was no association between measured JSW and CC at either the PFJ or TFJ. Both total osteophyte score and total number of sites with osteophyte were positively associated with CC; aOR for the upper quartile was 2.40 (1.48 to 3.90) and 1.94 (1.15 to 3.26), respectively. An association between CC and diuretic use was also demonstrated (aOR=2.07, 1.02 to 4.19). <b>Conclusions:</b> In this large UK community study the age, sex, and knee pain adjusted prevalence of CC was 4.5%. There was a strong age association, but no sex predisposition. Patellofemoral CC was uncommon. An association between OA and CC was confirmed, but this appears to operate through an association with osteophyte rather than JSN. The new association between CC and diuretic use might theoretically be explained by diuretic induced hypomagnesaemia.
Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: A prospective study
Authors: Yun-Fan Liaw, I-Shyan Sheen, Tong-Jong Chen, Chia-Ming Chu, Chia-C Pao
Journal: Hepatology (1991)

To investigate the incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection, a prospective follow-up study was conducted in two consecutive groups of patients. Group I consisted of 984 patients (859 men and 125 women) with biopsy-proven chronic type B hepatitis, whereas group II consisted of 1,598 asymptomatic chronic carriers (998 men and 600 women) with normal serum aminotransferase activity. During a mean follow-up period of 4.0 ± 2.3 yr, 19 patients (1.9%) of group I cleared HBsAg from their serum, whereas 35 patients (2.2%) in group II did so in a mean follow-up period of 2.7 ± 1.4 yr. The annual incidence of delayed serum HBsAg clearance was 0.5% in group I and 0.8% in group II (p &lt; 0.02). The cumulative probability of HBsAg clearance was also higher in group II than in group I (p &lt;0.007). Antibodies to HBsAg developed in 9 patients (47.4%) with chronic hepatitis and in 11 (31.4%) asymptomatic carriers who cleared serum HBsAg. Those who were HBeAg negative and those older than 40 at entry and those who exhibited cirrhosis during follow-up had a higher incidence of delayed HBsAg clearance. Gender, initial histological changes and hepatitis delta virus infection did not influence the occurrence of HBsAg clearance. Serum HBV DNA was not detectable by slot-blot hybridization but was still detectable by polymerase chain reaction in serum specimens collected within 1 yr of HBsAg clearance. Liver biopsy performed later in 10 patients showed no significant hepatitis activity or tissue HBV DNA, HBsAg or HBcAg. The results suggest that the incidence of delayed clearance of HBsAg during chronic HBV infection is low. HBeAg status, age of patients and development of cirrhosis are determinants for HBsAg clearance. (Hepatology 1991;13:627-631.)
Validity and repeatability of the IUATLD (1984) Bronchial Symptoms Questionnaire: an international comparison
Authors: PG Burney, LA Laitinen, S Perdrizet, H Huckauf, AE Tattersfield, S Chinn, N Poisson, A Heeren, None Britton, T Jones
Journal: European Respiratory Journal (1989)

The International Union against Tuberculosis and Lung Disease (IUATLD) Bronchial Symptoms Questionnaire (1984) was developed for use in studies of asthma and its reliability measured in an earlier survey in England. The association of the symptoms elicited by this questionnaire to bronchial response to histamine has also been described. This paper presents the results of studies of the questionnaire in four clinical centres in Europe. The reliability of the questionnaire and its ability to predict the bronchial response to histamine were compared for English, Finnish, French and German translations of the questionnaire in samples of diagnosed asthmatics and controls in Nottingham, Berlin, Helsinki and Paris. The answers to questions showed good repeatability, especially in Finland and Germany, particularly those questions on asthma and wheeze. The most sensitive symptom for predicting hyperresponsiveness was the question on wheeze, the most specific questions were those on waking at night with shortness of breath (Paris and Nottingham) and morning tightness (Helsinki and Berlin). This study shows that the IUATLD (1984) questionnaire may provide useful, valid and comparable data even in translation but these studies will need to be repeated in representative samples before such a possibility is accepted as fully demonstrated.
Effect of C-Peptide on Glucose Metabolism in Patients With Type 1 Diabetes
Authors: Thomas Forst, Klaus Rave, Andreas Pfuetzner, Ronald Buchholz, Thomas Pohlmann, Mirjam Löbig, Lutz Heinemann
Journal: Diabetes Care (2002)

In recent years, various biological activities of C-peptide have been confirmed, e.g., its ability to improve skin capillary blood flow in the feet, increase microvascular blood flow and oxygen uptake in the exercising forearm, decrease urinary albumin excretion, and improve nerve function in patients with type 1 diabetes (1,2). Furthermore, C-peptide stimulates glucose transport in human muscle strips of nondiabetic and diabetic subjects (3). Using a sequential insulin clamp technique, Li et al. (4) demonstrated that C-peptide in physiological concentrations stimulates body glucose utilization in diabetic rats. In a recent investigation by Grunberger et al. (5), C-peptide was shown to activate insulin receptor tyrosine kinase, insulin receptor substrate-1, tyrosine phosphorylation, phosphatidylinositol 3-kinase, mitogen-activated protein kinase phosphorylation, p90 Rsk (90-kDa ribosomal 56 protein kinase), and glycogen synthase kinase-3 phosphorylation. In addition, C-peptide mimics the effect of insulin, such as glycogen synthesis and amino acid uptake in rat muscle cells. However, in clinical studies involving C-peptide treatment for 1 or 3 months …
Ambient Pollution and Heart Rate Variability
Authors: Diane R. Gold, Augusto Litonjua, Joel Schwartz, Eric Lovett, Andrew Larson, Bruce Nearing, George Allen, Monique Verrier, Rebecca Cherry, Richard Verrier
Journal: Circulation (2000)

We investigated associations between ambient pollution levels and cardiovascular function in a repeated measures study including 163 observations on twenty-one 53- to 87-year-old active Boston residents observed up to 12 times from June to September 1997. Particles with aerodynamic diameter </=2.5 microm (PM(2.5)) were measured continuously using a tapered element oscillating microbalance.The protocol involved 25 minutes per week of continuous Holter ECG monitoring, including 5 minutes of rest, 5 minutes of standing, 5 minutes of exercise outdoors, 5 minutes of recovery, and 20 cycles of slow breathing. Heart rate variability (HRV) was assessed through time domain variables: the standard deviation of normal RR intervals (SDNN) and the square root of the mean of the squared differences between adjacent normal RR intervals (r-MSSD). Mean 4-hour PM(2.5) levels ranged from 3 to 49 microg/m(3); 1-hour ozone levels ranged from 1 to 77 ppb. In multivariate analyses, significantly less HRV (SDNN and r-MSSD) was associated with elevated PM(2.5). During slow breathing, a reduction in r-MSSD of 6.1 ms was associated with an interquartile (14.3 microg/m(3)) increase in PM(2.5) during the hour of and the 3 hours previous to the Holter session (P=0.006). During slow breathing, a multiple pollution model was associated with a reduction in r-MSSD of 5.4 ms (P=0.02) and 5.5 ms (P=0.03) for interquartile changes in PM(2.5) and ozone, respectively, resulting in a combined effect equivalent to a 33% reduction in the mean r-MSSD.Particle and ozone exposure may decrease vagal tone, resulting in reduced HRV.
Intraoperative Stem Cell Therapy
Authors: Mónica Beato Coelho, Joaquim M.S. Cabral, Jeffrey M. Karp
Journal: Annual Review of Biomedical Engineering (2012)

Stem cells hold significant promise for regeneration of tissue defects and disease-modifying therapies. Although numerous promising stem cell approaches are advancing in clinical trials, intraoperative stem cell therapies offer more immediate hope by integrating an autologous cell source with a well-established surgical intervention in a single procedure. Herein, the major developments in intraoperative stem cell approaches, from in vivo models to clinical studies, are reviewed, and the potential regenerative mechanisms and the roles of different cell populations in the regeneration process are discussed. Although intraoperative stem cell therapies have been shown to be safe and effective for several indications, there are still critical challenges to be tackled prior to adoption into the standard surgical armamentarium.
Incidence of Tuberculosis among a Cohort of Tuberculin-Positive Refugees in Australia
Authors: GUY B. MARKS, JUN BAI, SHEILA E. SIMPSON, ELIZABETH A. SULLIVAN, GREGORY J. STEWART
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Estimates of the lifetime risk of tuberculosis have varied widely and may not be applicable in all current settings. The aim of this study was to measure the incidence of reactivation of latent tuberculosis in a cohort of 15,489 predominantly Southeast Asian refugees aged 12 yr and over who arrived in Sydney, Australia during the period 1984 to 1994 and who had a clear chest X-ray on arrival. Tuberculin skin test (TST) reaction size and the presence of a BCG scar were recorded at entry. Incident cases of tuberculosis, occurring before June 1998, were identified by record linkage analysis with confirmatory review of case notes. There were 122 cases of tuberculosis over an average 10.3 yr of follow-up (crude annual incidence, 76.2/100,000). There was a linear increase in risk with increasing TST reaction size above 10 mm. The risk, and the relation of risk to TST reaction size, were unrelated to BCG scar status. Among those whose initial TST reaction was ⩾ 15 mm, the annual incidence rate in the first 3 yr was 213 (95% CI, 150 to 300) per 100,000 person-years and in the subsequent 10 yr the rate averaged 122 (95% CI, 90 to 165) per 100,000 person-years. The observed rates are similar to those estimated in the general population of the United States in the 1950s and 1960s. Further data on the prognosis of tuberculosis and the effects of isoniazid preventive therapy in Southeast Asian migrants to Western countries are required to inform policy and practice for the prevention of tuberculosis in this population.
The deceptive brain
Authors: S. A Spence
Journal: Journal of the Royal Society of Medicine (2003)

Why might deception be of interest to a clinical readership? Is it not a moral issue, more relevant to legal or theological discourse? How can we determine, scientifically, whether another human being is lying to us? Should we want to?

The answers to all of these questions might depend on the clinical setting envisaged. The significance of a lie about adherence to a treatment will depend on the clinical necessity of that treatment. In the forensic arena, a lie about plans for future conduct might have profound consequences: will the paedophile avoid playgrounds? In psychiatry, neurology, medicolegal practice and perhaps certain other areas of medicine, doctors are called upon to judge the veracity of their patient’s account (even though this may not be made explicit). Doctors commonly imply veracity in the terms that they use.

Consider the distinction between feigned physical symptoms (‘malingering’) and those ascribed to conversion disorder (‘hysteria’). These diagnoses have very different meanings, yet what objective grounds are there for differentiating between them?1 Notwithstanding the findings of brain imaging experiments,2 it would seem that, phenomenologically, there is little objective evidence that would favour one above the other, and the diagnosis reached may be influenced by circumstantial factors and the physician’s opinion of the patient’s personality or background. Also, the subtle ‘tricks’ used to elicit hysterical motor inconsistency (e.g. the unintentional movement of the ‘paralysed’ limb) might just as well be used to indicate deception.1,3 The point is not that these disorders are equivalent, rather that they lack objective differentiation. Yet, when recording these diagnoses, the physician implies whether the patient is to be believed.1

Are doctors especially good at detecting deception? This seems unlikely. When psychologists have studied various groups trying to decide whether others are lying to them, doctors have performed at the level of chance;4,5 with the possible exception of security personnel, it seems to make little difference whether the putative ‘lie detector’ is a judge, a police officer or a doctor.

However, there is a more subtle aspect to deception that emerges when human behaviour is conceptualized in terms of its higher, executive, control processes. For it would appear that deception ‘behaves’ as if it is a skill—something that must be worked at, for which attention is required, and in which fatigue may lead to inconsistency or unintended confession.5

The question of whether lying relies upon higher brain systems is important because such systems may be differentially affected in neuropsychiatric disorders. In the case of some of the most difficult patients with whom psychiatrists interact (such as ‘psychopaths’ and sex offenders), deception may be a feature of that interaction. A psychopath who is a skilled liar may be demonstrating preserved, or possibly superior, executive brain function. This may have profound implications for our understanding of responsibility and mitigation.
Enhanced B-cell differentiation and reduced proliferative capacity in chronic hepatitis C and chronic hepatitis B virus infections
Authors: Barbara Oliviero, Antonella Cerino, Stefania Varchetta, Enrica Paudice, Somnath Pai, Serena Ludovisi, Marco Zaramella, Giuseppe Michelone, Paolo Pugnale, Francesco Negro, Vincenzo Barnaba, Mario U. Mondelli
Journal: Journal of Hepatology (2010)
A dominant hepatitis B virus population defective in virus secretion because of several S-gene mutations from a patient with fulminant hepatitis
Authors: Tatyana Kalinina, Anna Riu, Lutz Fischer, Hans Will, Martina Sterneck
Journal: Hepatology (2001)

There is increasing evidence that certain pathogenic hepatitis B virus (HBV) variants may play a role in the pathogenesis of fulminant hepatitis (FHB). Recently, we isolated from a patient with fulminant recurrent hepatitis B after liver transplantation variants with enhanced replication competence and a possible defect in viral particle secretion. Both viral features may have contributed to the severity of the disease. The aim of this study was to prove the secretion defect of these variants, to analyze the consequences, and to identify the responsible viral mutations. The variant genomes and appropriate wild–type/variant hybrid genomes were functionally characterized after transfection in human hepatoma cells. Two cloned genomes and the polymerase chain reaction (PCR)–amplified mixture of full–length genomes showed a block in viral particle secretion. This was caused by a combination of amino acid changes in the S–protein including the mutation G145R frequently emerging after hyperimmunoglobulin treatment. The mutations induced retention of the surface proteins in an endoplasmic reticulum (ER)–like compartment, but no intracellular accumulation. These data provide evidence for the in vivo existence of a dominant HBV population with a severe defect in viral particle secretion caused by mutations in the S–gene. This viral phenotype in combination with the enhanced replication competence may have contributed to the fulminant clinical course of the infection.
Central Nervous System (CNS) Relapse Following Chemotherapy of WF Rat Acute Myelogenous Leukemia: A Model for Human CNS Leukemia2
Authors: Joel S. Greenberger, Mary B. Muse, Carol A. Bocaccino, William C. Moloney
Journal: JNCI Journal of the National Cancer Institute (1977)

The treatment of central nervous system (CNS) involvement in human acute myelogenous leukemia (AML) presents a serious therapeutic dilemma. In an attempt to study the pathophysiology of this diseases in an animal model, the incidence and sites of detection of CNS leukemia were evaluated in inbred rats receiving chemotherapy for the transplantable WF AML. Eight of 100 rats with untreated WF AML demonstrated CNS leukemia at death with concomitant widespread visceral infiltrates, ascites, bone marrow involvement, and peripheral blood leukemia. Similarly, 6 of 120 rats (5%) failing to attain a complete remission following adriamycin. Cytoxan, or cytosine arabinoside chemotherapy demonstrated CNS leukemia in addition to systemic disease at death. In contrast, 70 of 75 rats (93.3%) achieving a complete remission subsequently relapsed in the CNS, either in combination with widespread systemic disease in 48 (64.0%) or with minimal evidence of systemic relapse in 22 (29.3%). There was a greater frequency of detectable cerebral compared to spinal cord infiltrates in relapsing rats. The WF AML appears to be a valuable model for study of the mechanism and ultimately the prevention of CNS relapse following chemotherapy in human AML.
Anti-cholinergic effects of quinidine, disopyramide, and procainamide in isolated atrial myocytes: mediation by different molecular mechanisms.
Authors: T Nakajima, Y Kurachi, H Ito, R Takikawa, T Sugimoto
Journal: Circulation Research (1989)

Effects of quinidine, disopyramide, and procainamide on the acetylcholine (ACh)-induced K+ channel current were examined in single atrial cells, using the tight-seal, whole-cell clamp technique. The pipette solution contained guanosine-5'-triphosphate (GTP) or guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma S, a nonhydrolysable GTP analogue). In GTP-loaded cells, not only ACh but also adenosine induced a specific K+ channel current via GTP-binding proteins (G) by activating muscarinic ACh or adenosine receptors. Quinidine and disopyramide depressed the ACh-induced K+ current quite effectively. Procainamide had a weak inhibitory effect. Quinidine also depressed adenosine-induced K+ current, while the effect of disopyramide on adenosine-induced current was much smaller than that on ACh-induced current. In GTP-gamma S-loaded cells, the K+ channel was uncoupled from the receptors and was activated irreversibly, probably due to direct activation of G proteins by GTP-gamma S. Quinidine depressed the GTP-gamma S-induced K+ current just as in the cases of ACh- and adenosine-induced currents of GTP-loaded cells. Disopyramide had only a weak inhibitory effect and procainamide showed no effect. From these results, it is strongly suggested that the major mechanisms underlying the anti-cholinergic effects of quinidine, disopyramide, and procainamide are different; quinidine may inhibit the muscarinic K+ channel itself and/or G proteins, while disopyramide and high doses of procainamide may mainly block functions of muscarinic ACh receptors in atrial myocytes.
Impaired T-Independent IgM Responses Due To Irak-4-, MyD88 Deficiency Or Splenectomy
Authors: Paul J. Maglione, Lin Radigan, Sam Black, Jessica Overbey, Emelia Bagiella, Isabelle Meyts, Jean-Laurent Casanova, Capucine Picard, Charlotte Cunningham-Rundles
Journal: Journal of Allergy and Clinical Immunology (2014)