tbuckley/cabot-search huggingface dataset:
Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial
Authors: Antonio Palumbo, Sara Bringhen, Tommaso Caravita, Emanuela Merla, Vincenzo Capparella, Vincenzo Callea, Clotilde Cangialosi, Mariella Grasso, Fausto Rossini, Monica Galli, Lucio Catalano, Elena Zamagni, Maria Teresa Petrucci, Valerio De Stefano, Manuela Ceccarelli, Maria Teresa Ambrosini, Ilaria Avonto, Patrizia Falco, Giovannino Ciccone, Anna Marina Liberati, Pellegrino Musto, Mario Boccadoro
Journal: The Lancet (2006)
Isotretinoin-induced elkonyxis
Authors: A. Yung, P. Johnson, M.J.D. Goodfield
Journal: British Journal of Dermatology (2005)

Journal Article Isotretinoin‐induced elkonyxis Get access A. Yung, A. Yung Department of Dermatology, Leeds General Infirmary, Leeds LS1 3EX, U.K. E‐mail: Anthony.Yung@leedsth.nhs.uk; ants_ange@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar P. Johnson, P. Johnson Department of Dermatology, Leeds General Infirmary, Leeds LS1 3EX, U.K. E‐mail: Anthony.Yung@leedsth.nhs.uk; ants_ange@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar M.J.D. Goodfield M.J.D. Goodfield Department of Dermatology, Leeds General Infirmary, Leeds LS1 3EX, U.K. E‐mail: Anthony.Yung@leedsth.nhs.uk; ants_ange@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 3, 1 September 2005, Pages 671–672, https://doi.org/10.1111/j.1365-2133.2005.06782.x Published: 01 September 2005
Benefits of physical activity on COPD hospitalisation depend on intensity
Authors: David Donaire-Gonzalez, Elena Gimeno-Santos, Eva Balcells, Jordi de Batlle, Maria A. Ramon, Esther Rodriguez, Eva Farrero, Marta Benet, Stefano Guerra, Jaume Sauleda, Antoni Ferrer, Jaume Ferrer, Joan A. Barberà, Robert Rodriguez-Roisin, Joaquim Gea, Alvar Agustí, Josep M. Antó, Judith Garcia-Aymerich
Journal: European Respiratory Journal (2015)

The present study aims to disentangle the independent effects of the quantity and the intensity of physical activity on the risk reduction of chronic obstructive pulmonary disease (COPD) hospitalisations.177 patients from the Phenotype Characterization and Course of COPD (PAC-COPD) cohort (mean±sd age 71±8 years, forced expiratory volume in 1 s 52±16% predicted) wore the SenseWear Pro 2 Armband accelerometer (BodyMedia, Pittsburgh, PA, USA) for eight consecutive days, providing data on quantity (steps per day, physically active days and daily active time) and intensity (average metabolic equivalent tasks) of physical activity. Information on COPD hospitalisations during follow-up (2.5±0.8 years) was obtained from validated centralised datasets. During follow-up 67 (38%) patients were hospitalised. There was an interaction between quantity and intensity of physical activity in their effects on COPD hospitalisation risk. After adjusting for potential confounders in the Cox regression model, the risk of COPD hospitalisation was reduced by 20% (hazard ratio (HR) 0.79, 95% CI 0.67-0.93; p=0.005) for every additional 1000 daily steps at low average intensity. A greater quantity of daily steps at high average intensity did not influence the risk of COPD hospitalisations (HR 1.01, p=0.919). Similar results were found for the other measures of quantity of physical activity. Greater quantity of low-intensity physical activity reduces the risk of COPD hospitalisation, but high-intensity physical activity does not produce any risk reduction.
Biosynthesis and degradation of hyaluronan by nonparenchymal liver cells during liver regeneration
Authors: D Vrochides, V Papanikolaou, H Pertoft, A A Antoniades, P Heldin
Journal: Hepatology (1996)

Hepatic stellate cells (HSC) and endothelial cells of the liver sinusoids synthesize and degrade hyaluronan, respectively. The roles of these cell types in the biosynthesis and degradation of hyaluronan were studied during regeneration following partial hepatectomy. Pure cultures of HSC and liver endothelial cells (LEC) were obtained from regenerating liver at different stages using a Nycodenz gradient followed by discontinuous Percoll gradient. The HSC that established 3 or 4 days after partial hepatectomy synthesized large amounts of hyaluronan when cultured in the presence of fetal calf serum (FCS) or platelet–derived growth factor B–chain homodimer (PDGF)–BB. These cells, as well as LEC, expressed active PDGF β–receptors. Furthermore, the ability of LEC to degrade hyaluronan was decreased at early stages of liver regeneration. The increased synthesis of hyaluronan by HSC and the failure of LEC to catabolize the polysaccharide resulted in elevated hyaluronan concentrations in the blood.
The Rexinoid LG100268 Prevents the Development of Preinvasive and Invasive Estrogen Receptor–Negative Tumors in MMTV-erbB2 Mice
Authors: Yuxin Li, Yun Zhang, Jamal Hill, Qiang Shen, Hee-Tae Kim, Xiaochun Xu, Susan G. Hilsenbeck, Reid P. Bissonnette, William W. Lamph, Powel H. Brown
Journal: Clinical Cancer Research (2007)

To test whether a novel rexinoid, LG100268, prevents the development of preinvasive and invasive estrogen receptor-negative mammary tumorigenesis in MMTV-erbB2 mice.For invasive breast cancer prevention, MMTV-erbB2 mice were treated with daily gastric gavage of vehicle, LG100268 (10 mg/kg), or LG100268 (100 mg/kg) for long term starting at 3 months of age. For preinvasive lesion study, mice were treated with daily gastric gavage of vehicle or LG100268 (100 mg/kg) for 4 months.Long-term treatment with LG100268 significantly prevented invasive mammary tumor development. Median time (age) to tumor development was delayed from 217 days in vehicle group to 357 days in low-dose group. In high-dose group, only 2 of 20 mice developed tumors after 430 days of treatment. Short-term treatment of LG100268 significantly prevented the development of preinvasive mammary lesions including hyperplasia and ductal carcinoma in situ. The cancer prevention effect was associated with reduced expression of Ki67 and cyclin D1 in mammary glands by >80%.Rexinoid LG100268 is an effective chemopreventive agent in preventing the development of both malignant and premalignant mammary lesions in MMTV-erbB2 mice.
Capacity of the Terminal Vascular Bed during Normal Growth, in Cardiomegaly, and in Cardiac Atrophy
Authors: KAREL RAKUšan, WOLFGANG DU MESNIL DE ROCHEMONT, WOLFGANG BRAASCH, HANS TSCHOPP, RICHARD J. BING
Journal: Circulation Research (1967)

Vascular capacity representing the terminal vascular bed was determined by albumin 131 I in the rabbit myocardium during normal and pathological growth of the heart. A considerable increase in the vascular capacity in the first postnatal weeks indicated growth of the terminal vascular bed during this period. Highest values were reached in animals approximately 6 weeks old. From this time, vascular capacity gradually decreased in relation to the increase in heart and body weight. The growth rate of the terminal vascular bed was very rapid during the first postnatal weeks and later became slower; no growth was detected in adult and old animals. Growth of the terminal vascular bed during pathological increase in heart weight followed the same trend. In young animals pathological growth of the heart was accompanied by an increase in the capacity of the terminal vascular bed; in adult animals the total capacity remained unchanged. A decrease in heart weight in animals kept on a protein-free diet was characterized by a relatively small vascular capacity.
Eradication of Helicobacter pylori restores the inhibitory effect of cholecystokinin on postprandial gastrin release in duodenal ulcer patients.
Authors: J W Konturek, A Gillessen, S J Konturek, W Domschke
Journal: Gut (1995)

Helicobacter pylori infection may be associated with duodenal ulcer (DU) and accompanied by enhanced gastrin release but the mechanism of this H pylori related hypergastrinaemia in DU patients is unclear. Cholecystokinin (CCK) has been implicated in the feedback control of gastrin release and gastric acid secretion in healthy subjects. This study therefore investigated if CCK participates in the impairment of postprandial gastrin release and gastric secretion in six DU patients. Tests were undertaken with and without elimination of endogenous CCK by loxiglumide, a selective CCK-A receptors antagonist, before and after eradication of H pylori with triple therapy (omeprazole, amoxicyllin, bismuth). In H pylori positive DU patients, the post-prandial decline in pH (with median pH 3.5) was accompanied by a pronounced increment in plasma gastrin but the administration of loxiglumide did not affect significantly this postprandial rise in plasma gastrin and gastric pH profile. After eradication of H pylori, the plasma gastrin concentration was reduced while the median postprandial pH was significantly increased (median pH 4.3). The administration of loxiglumide resulted in significantly greater increase in postprandial plasma gastrin and greater decrease in pH (median pH 3.1) in these patients. This study shows that (a) infection with H pylori is accompanied by an enhanced gastrin release and gastric acidity in DU patients, (b) the failure of loxiglumide to affect plasma gastrin or gastric acid secretion in H pylori infected DU patients could be attributed, at least in part, to the failure of endogenous CCK to control gastrin release and gastric secretion by releasing somatostatin, and (c) the test with loxiglumide may be useful in the identification of patients with impaired feedback control of gastrin release and gastric secretion resulting from infection with H pylori.
Making Advances in First-Line Chronic Lymphocytic Leukemia Treatment
Authors: William G. Wierda
Journal: Journal of Clinical Oncology (2012)

Bendamustine was developed in East Germany as a potent alkylating agent. Bendamustine monotherapy was US Food and Drug Administration approved for both first-line and salvage treatment of patients with chronic lymphocytic leukemia (CLL) as a result of superior progression-free survival (PFS) compared with that seen with chlorambucil monotherapy in first-line treatment of CLL. Although CD20 monoclonal antibody (mAB) monotherapy has limited activity in CLL, the German CLL Study Group (GCLLSG) confirmed in their CLL8 trial that the addition of rituximab to chemotherapy significantly advanced treatment for CLL, with improved PFS and overall survival (OS). On the basis of these data and data from the REACH (Rituximab in the Study of Relapsed Chronic Lymphocytic Leukemia) trial, rituximab was US Food and Drug Administration approved in combination with fludarabine and cyclophosphamide (FC) for firstline and previously treated CLL. The GCLLSG reported results of a phase II trial of bendamustine combined with rituximab (BR) for relapsed and refractory CLL, and in the article that accompanies this editorial, Fischer et al, on behalf of the GCLLSG, report results of a first-line, multicenter phase II clinical trial of BR for CLL. They report an overall response rate of 88%, complete remission (CR) rate of 23%, and estimated median PFS of 34 months for 117 previously untreated patients with CLL. Grade 3 or 4 neutropenia, thrombocytopenia, and anemia occurred in 20%, 22%, and 20% of patients, respectively. Randomized first-line phase III clinical trials that evaluated chlorambucil versus fludarabine, then fludarabine versus FC, and most recently, FC versus FC plus rituximab (FCR), established FCR as a standard chemoimmunotherapy (CIT) regimen that provides excellent PFS and OS. Other agents have been evaluated in phase III trials as monotherapy compared with chlorambucil, such as alemtuzumab and bendamustine, and have garnered US Food and Drug Administration approval on the basis of superior PFS, but hardly represent significant therapeutic advances. Several phase II trials have aimed to improve outcomes by modifying FCR, but without obvious success. Examples include increasing the dose of rituximab, adding mitoxantrone, adding alemtuzumab, or adding a granulocytemacrophage colony-stimulating factor to the FCR regimen. These first-line phase II BR trial results can be compared with standard first-line CD20 mAb–containing CIT regimens like FCR, FR, or pentostatin, cyclophosphamide, and rituximab (Table 1). The difficulty in comparing outcomes between clinical trials is that
Model System to Define Pharmacokinetic Requirements for Antimalarial Drug Efficacy
Authors: Rahul P. Bakshi, Elizabeth Nenortas, Abhai K. Tripathi, David J. Sullivan, Theresa A. Shapiro
Journal: Science Translational Medicine (2013)

Malaria presents a tremendous public health burden, and new therapies are needed. Massive compound libraries screened against Plasmodium falciparum have yielded thousands of lead compounds, resulting in an acute need for rational criteria to select the best candidates for development. We reasoned that, akin to antibacterials, antimalarials might have an essential pharmacokinetic requirement for efficacy: action governed either by total exposure or peak concentration (AUC/CMAX), or by duration above a defined minimum concentration [time above minimum inhibitory concentration (TMIC)]. We devised an in vitro system for P. falciparum, capable of mimicking the dynamic fluctuations of a drug in vivo. Using this apparatus, we find that chloroquine is TMIC-dependent, whereas the efficacy of artemisinin is driven by CMAX. The latter was confirmed in a mouse model of malaria. These characteristics can explain the clinical success of two antimalarial drugs with widely different kinetics in humans. Chloroquine, which persists for weeks, is ideally suited for its TMIC mechanism, whereas great efficacy despite short exposure (t1/2 in blood 3 hours or less) is attained by CMAX-driven artemisinins. This validated preclinical model system can be used to select those antimalarial lead compounds whose CMAX or TMIC requirement for efficacy matches pharmacokinetics obtained in vivo. The apparatus can also be used to explore the kinetic dependence of other pharmacodynamic endpoints in parasites.
Comments on ‘Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia’ by Vanheel<i>et al</i>
Authors: L Rodrigo, E Lauret, I Pérez, A Suárez
Journal: Gut (2014)

We note with great interest the finding by Vanheel et al of increased intestinal permeability in a series of patients with functional dyspepsia (FD). This represents an important contribution to the study of this disease.1 This has previously been observed in patients with IBS, which has led researchers to consider whether the two disorders, customarily considered to be functional, might have an underlying organic basis.2 

Nevertheless, we find the information provided about the patient selection criteria to be insufficient, and we would like a complementary explanation of this matter.

The 15 patients with FD included in this study were all negative for Helicobacter pylori . The fulfilment of this requirement may partially account for the small sample, but we would be in a better position to judge this if we knew the mean prevalence of H pylori infection in the adult population of Belgium, how many patients in the series had previously received eradication therapy, the time elapsed before their inclusion in the study and the detection method used. The authors …
Cardiac involvement and treatment-related mortality after non-myeloablative haemopoietic stem-cell transplantation with unselected autologous peripheral blood for patients with systemic sclerosis: a retrospective analysis
Authors: Richard K Burt, Maria Carolina Oliveira, Sanjiv J Shah, Daniela A Moraes, Belinda Simoes, Mihai Gheorghiade, James Schroeder, Eric Ruderman, Dominique Farge, Z Jessie Chai, Zora Marjanovic, Sandeep Jain, Amy Morgan, Francesca Milanetti, Xiaoqiang Han, Borko Jovanovic, Irene B Helenowski, Julio Voltarelli
Journal: The Lancet (2013)
A Nongenomic Mechanism for Progesterone-mediated Immunosuppression: Inhibition of K+ Channels, Ca2+ Signaling, and Gene Expression in T Lymphocytes
Authors: George R. Ehring, Hubert H. Kerschbaum, Claudia Eder, Amber L. Neben, Christopher M. Fanger, Rosana M. Khoury, Paul A. Negulescu, Michael D. Cahalan
Journal: The Journal of Experimental Medicine (1998)

The mechanism by which progesterone causes localized suppression of the immune response during pregnancy has remained elusive. Using human T lymphocytes and T cell lines, we show that progesterone, at concentrations found in the placenta, rapidly and reversibly blocks voltage-gated and calcium-activated K+ channels (KV and KCa, respectively), resulting in depolarization of the membrane potential. As a result, Ca2+ signaling and nuclear factor of activated T cells (NF-AT)-driven gene expression are inhibited. Progesterone acts distally to the initial steps of T cell receptor (TCR)-mediated signal transduction, since it blocks sustained Ca2+ signals after thapsigargin stimulation, as well as oscillatory Ca2+ signals, but not the Ca2+ transient after TCR stimulation. K+ channel blockade by progesterone is specific; other steroid hormones had little or no effect, although the progesterone antagonist RU 486 also blocked KV and KCa channels. Progesterone effectively blocked a broad spectrum of K+ channels, reducing both Kv1.3 and charybdotoxin–resistant components of KV current and KCa current in T cells, as well as blocking several cloned KV channels expressed in cell lines. Progesterone had little or no effect on a cloned voltage-gated Na+ channel, an inward rectifier K+ channel, or on lymphocyte Ca2+ and Cl− channels. We propose that direct inhibition of K+ channels in T cells by progesterone contributes to progesterone-induced immunosuppression.
Length of excitation wave and susceptibility to reentrant atrial arrhythmias in normal conscious dogs.
Authors: P L Rensma, M A Allessie, W J Lammers, F I Bonke, M J Schalij
Journal: Circulation Research (1988)

We calculated the wavelength of the atrial impulse in chronically instrumented conscious dogs by measuring both conduction velocity and refractory period: wavelength = refractory period X conduction velocity. Implantation of multiple stimulating and recording electrodes allowed wavelength determination at four different areas: the right and left parts of Bachmann's bundle and the free walls of the right and left atria. During programmed electrical stimulation, three types of arrhythmias were observed: rapid repetitive responses, atrial flutter, and atrial fibrillation. During normal rhythm, the wavelength of the atrial impulse varied between 14 and 18 cm. Premature beats had a shorter wavelength, depending on the degree of prematurity. Premature beats that evoked rapid repetitive responses showed a critical shortening of the wavelength below 12.3 cm. Episodes of atrial flutter were induced at a wavelength below 9.7 cm, while fibrillation occurred at wavelengths shorter than 7.8 cm. We correlated the induction of these arrhythmias with the values of refractory period, conduction velocity, and wavelength during control and during administration of several drugs. Intravenous administration of acetylcholine shortened the wavelength by 30-40%, mainly because of refractory period shortening. Both propafenone and lidocaine had strong but opposite effects on refractoriness and conduction and, consequently, little effect on the wavelength. Quinidine markedly prolonged the refractory period, but prolongation of wavelength was less because of a simultaneous decrease in conduction velocity. d-Sotalol also increased refractory period, but because it had no appreciable effect on conduction velocity, this drug was the most effective in prolongation of wavelength. Linear discriminant analysis of the data showed that the refractory period and the conduction velocity each were poor parameters to predict the occurrence of the different arrhythmias (predictive value 48% and 38%, respectively). The combination of both properties, however, as expressed in the wavelength, was a more reliable index that predicted the induction of the different arrhythmias correctly in 75% of the cases. We conclude that the wavelength is a useful parameter for evaluating antiarrhythmic drugs.
Antiretroviral therapy for prevention of HIV transmission: implications for Europe
Authors: V Cambiano, J O’Connor, A N Phillips, A Rodger, R Lodwick, A Pharris, F Lampe, F Nakagawa, C Smith, M J van de Laar
Journal: Eurosurveillance (2013)

The aim of this review is to summarise the evidence on the population-level effect of antiretroviral therapy (ART) in preventing HIV infections, and to discuss potential implications in the European context of recommending starting ART when the CD4 count is above 350 cells/mm 3 . The ability of ART to reduce the risk of HIV transmission has been reported in observational studies and in a randomised controlled trial (HPTN 052), in which ART initiation reduced HIV transmission by 96% within serodiscordant couples. As yet, there is no direct evidence for such an effect among men having sex with men or people who inject drugs. HPTN 052 led international organisations to develop recommendations with a higher CD4 threshold for ART initiation. However, there remains a lack of strong evidence of clinical benefit for HIV-positive individuals starting ART with CD4 count above 350 cells/mm 3 . The main goal of ART provision should be to increase ART coverage for all those in need, based on the current guidelines, and the offer of ART to those who wish to reduce infectivity; increased HIV testing is therefore a key requirement. Other proven prevention means such as condom use and harm reduction for people who inject drugs remain critical.
A STUDY OF THE MINNESOTA MULTIPHASIC PERSONALITY INVENTORY IN CLINICAL PRACTICE
Authors: HERBERT C. MODLIN
Journal: American Journal of Psychiatry (1947)

1. The Minnesota Multiphasic Personality Inventory (M. Inventory) was evaluated by application to 416 United States Army enlisted personnel. Results in this study present convincing evidence that the test is a valuable psychometric adjunct to clinical psychiatric practice. 2. It does not establish definitive diagnoses; it sometimes overemphasizes certain personality distortions and minimizes others; it requires interpretation in the light of the total clinical picture; it is not a substitute for the psychiatrist. 3. Anxiety may be satisfactorily measured by averaging the scores of the first three M. Inventory scales, hypochondriasis (Hs), depression (D), and hysteria (Hy), to form an A (anxiety) score. 4. The M. Inventory elicits significant data in several psychosomatic illnesses. In migraine, post-traumatic headache, epilepsy, somnambulism and enuresis it meets clinical expectations to a high degree. 5. M. Inventory retests at intervals prove dependable in following the clinical course and helpful in determining the prognosis. 6. The M. Inventory makes its most constructive contribution to clinical medicine in illuminating the study of individual cases through combinations of its multiple scores which reveal many facets of the disturbed personality. Technical assistance was rendered by Sgt. Robert Stewart, Sgt. Alvin Brookman, and Cpl. Sidney Noble.