tbuckley/cabot-search huggingface dataset:
The treatment of lupus nephritis
Authors: David P D'Cruz, Graham R V Hughes
Journal: BMJ (2005)

1918-9, for example, killed an estimated 40-50 million people.Research into influenza, in relation to its catastrophic potential, is underfunded. 2Worse still, we do not even seem able to provide sufficient vaccine to control epidemic influenza in the most developed countries.Little confidence exists that we could undertake a global immunisation programme for an influenza pandemic even if we had sufficient warning of its antigenic profile unless we can sharpen up on manufacture and distribution.Other notable examples of neglected diseases afflicting the world include antibacterial drug resistance, chronic obstructive pulmonary disease, alcoholic liver disease, and stroke. 1 Secondly, the pharmaceutical industry is clearly unable to meet the needs of people with neglected diseases.This is not a criticism but a fact, for the pharmaceutical industry is a business and needs to provide its shareholders with a return on their investment.Many neglected diseases are unlikely to to do this and investment represents a great commercial risk.The industry will continue to play a major part in the discovery and development of drugs; but we need much greater pluralism in both the funding and discovery of novel treatments.Examples of this pluralistic approach already exist.Substantial public funds for basic and clinical research, ultimately aimed at producing new forms of treatment, are available in the United States and to a lesser extent in Europe.The research agenda in the WHO report should be a major feature of the European Union's next research programme.For this we must rely on the influence of the Dutch presidency.But Europe also needs to harness the potential of public-private partnerships along the lines of the Global Alliance for TB Drug Development, or the Hereditary Disease Foundation in the United States. 3Public-private partnerships involve joint investment of resources by bodies including universities, government supported research organisations, pharmaceutical companies, venture capitalists, and research based charities.The Hereditary Disease Foundation's public-private partnerships include, for example, not only the foundation itself but several pharmaceutical companies and academic researchers of the Huntington Study Group collectively seeking an effective treatment for Huntington's disease; and that of the Global Alliance for TB Drug Development is a joint initiative between the Rockefeller Foundation, the Bill and Melinda Gates Foundation, WHO, a group of university based investigators, and several private companies. 3hirdly, the cost of developing a new drug must be reduced. 4Unless savage cuts can be made in the
Sex Differences in the Functional Neuroanatomy of Working Memory in Adults With ADHD
Authors: Eve M Valera, Ariel Brown, Joseph Biederman, Stephen V. Faraone, Nikos Makris, Michael C. Monuteaux, Susan Whitfield-Gabrieli, Michael Vitulano, Michael Schiller, Larry J. Seidman
Journal: American Journal of Psychiatry (2009)

Objective Although attention deficit hyperactivity disorder (ADHD) in adults is associated with significant morbidity and dysfunction and afflicts both sexes, relatively few imaging studies have examined female subjects and none have had sufficient power to adequately examine sex differences. The authors examined sex differences in the neural functioning of adults with ADHD during performance of a verbal working memory task. Method The participants were 44 adults with ADHD matched on age, sex, and estimated IQ to 49 comparison subjects. Accuracy and reaction time on an N-back task were measured to assess working memory. The blood-oxygen-level-dependent functional MRI response was used as a measure of neural activity. Results A group-by-sex analysis of variance showed no between-group differences in either reaction time or percent correct for the working memory task. For both sexes combined, the adults with ADHD showed less activity than comparison subjects in prefrontal regions. However, sex-by-group analyses revealed an interaction, such that male ADHD subjects showed significantly less activity in right frontal, temporal, and subcortical regions and left occipital and cerebellar regions relative to male comparison subjects, whereas female ADHD subjects showed no differences from female comparison subjects. Exploratory correlation analyses revealed negative associations between working-memory-related activation and number of hyperactive symptoms for men and number of inattentive symptoms for women. Conclusions Male but not female adults with ADHD showed significantly altered patterns of neural activity during a verbal working memory task. Men and women showed different associations between neural activity and ADHD symptoms.
Lifestyle interventions for knee pain in overweight and obese adults aged &gt;=45: economic evaluation of randomised controlled trial
Authors: G. R Barton, T. H Sach, C. Jenkinson, M. Doherty, A. J Avery, K. R Muir
Journal: BMJ (2009)

<b>Objective</b> To estimate the cost effectiveness of four different lifestyle interventions for knee pain. <b>Design</b> Cost utility analysis of randomised controlled trial. <b>Setting</b> Five general practices in the United Kingdom. <b>Participants</b> 389 adults aged ≥45 with self reported knee pain and body mass index (BMI) ≥28. <b>Interventions</b> Dietary intervention plus quadriceps strengthening exercises, dietary intervention, quadriceps strengthening exercises, and leaflet provision. Participants received home visits over a two year period. <b>Main outcome measure</b> Incremental cost per quality adjusted life year (QALY) gained over two years from a health service perspective. <b>Results</b> Advice leaflet was associated with a mean change in cost of −£31, and a mean QALY gain of 0.085. Both strengthening exercises and dietary intervention were more effective (0.090 and 0.133 mean QALY gain, respectively) but were not cost effective. Dietary intervention plus strengthening exercises had a mean cost of £647 and a mean QALY gain of 0.147 and was estimated to have an incremental cost of £10 469 per QALY gain (relative to leaflet provision), and a 23.1% probability of being cost effective at a £20 000/QALY threshold. <b>Conclusion</b> Dietary intervention plus strengthening exercises was estimated to be cost effective for individuals with knee pain, but with a large level of uncertainty. <b>Trial registration</b>ISRCTN93206785.
Coronary dilation with standard dose dipyridamole and dipyridamole combined with handgrip.
Authors: J D Rossen, I Simonetti, M L Marcus, M D Winniford
Journal: Circulation (1989)

Intravenous dipyridamole is widely used to produce coronary vasodilation during cardiac imaging procedures. However, the routinely used dose of dipyridamole (0.56 mg/kg IV over 4 min) does not always result in maximal coronary dilation. The addition of isometric handgrip during dipyridamole coronary dilation has been reported to substantially increase coronary blood flow over dipyridamole alone. We compared the coronary vasodilation resulting from infusion of the standard dose of dipyridamole with that resulting from a maximally dilating dose of intracoronary papaverine in 12 patients with angiographically normal coronary arteries. We also assessed the effect on coronary blood flow velocity of the addition of isometric handgrip during dipyridamole coronary dilation. Changes in coronary blood flow velocity were measured with a 3F coronary Doppler catheter. The coronary flow reserve (peak/resting coronary flow velocity ratio) after dipyridamole (3.7 +/- 1.2 [mean +/- SD] was less than that seen after papaverine (4.4 +/- 0.5, p less than 0.05), and the coronary vascular resistance index during dipyridamole coronary vasodilation (0.28 +/- 0.09) was greater than during papaverine (0.22 +/- 0.03, p less than 0.05). The dipyridamole coronary flow reserve was less than 3.0 in four subjects and was 2.0 or less in two subjects. The addition of isometric handgrip to dipyridamole coronary vasodilation produced an 8% increase in mean heart rate and a 17% increase in mean arterial pressure, but coronary flow reserve was unchanged (3.8 +/- 1.1 before handgrip vs. 4.0 +/- 1.1 with handgrip). Quantitative angiography in six patients revealed no change in coronary caliber with the addition of handgrip.(ABSTRACT TRUNCATED AT 250 WORDS)
A phase II study of gemcitabine in platinum pre-treated patients with advanced epithelial ovarian cancer
Authors: M. Friedlander, M.J. Millward, D. Bell, R. Bugat, P. Harnett, J.A. Moreno, L. Campbell, C. Varette, V. Ripoche, L. Kayitalire
Journal: Annals of Oncology (1998)
Molecular basis of an autoantibody-associated restriction fragment length polymorphism that confers susceptibility to autoimmune diseases.
Authors: T Olee, P M Yang, K A Siminovitch, N J Olsen, J Hillson, J Wu, F Kozin, D A Carson, P P Chen
Journal: Journal of Clinical Investigation (1991)

Recently, combined serological and molecular studies of autoantibodies have revealed that these antibodies play an important role in the normal function of the immune system and in the development of the B cell repertoire. Accordingly, we hypothesized that a homozygous deletion of a critical autoantibody-associated Ig variable (V) gene may alter the immune system and thus predispose the host to autoimmune disorders. Initial experiments revealed several restriction fragment length polymorphisms (RFLP) of the Humhv3005 gene, that is likely to encode heavy chains of rheumatoid factors, and the closely related 1.9III gene. By probing EcoR1-digested DNA with the Humhv3005/P1 probe, we found that one of the four major hybridizing bands was missing in approximately 20% of patients with either rheumatoid arthritis or systemic lupus erythematosus, but only 2% of normal subjects. To delineate the genetic basis of this polymorphism, we have now employed the PCR to amplify and analyze hv3005, 1.9III, and homologous genes in individuals with characteristic RFLP genotypes. Our results indicate that the human Vh gene repertoire contains several hv3005- and 1.9III-like genes, and that a complete deletion of the hv3005-like genes is relatively restricted to a subset of autoimmune patients. These findings provide initial evidence for deletion of developmentally regulated autoreactive V genes in autoimmune diseases.
Microarray Analysis of Endometrial Carcinomas and Mixed Mullerian Tumors Reveals Distinct Gene Expression Profiles Associated with Different Histologic Types of Uterine Cancer
Authors: G. Larry Maxwell, G.V.R. Chandramouli, Lou Dainty, Tracy J. Litzi, Andrew Berchuck, J. Carl Barrett, John I. Risinger
Journal: Clinical Cancer Research (2005)

Previous studies using cDNA microarray have indicated that distinct gene expression profiles characterize endometrioid and papillary serous carcinomas of the endometrium. Molecular studies have observed that mixed mullerian tumors, characterized by both carcinomatous and sarcomatous components, share features that are characteristic of endometrial carcinomas. The objective of this analysis was to more precisely define gene expression patterns that distinguish endometrioid and papillary serous histologies of endometrial carcinoma and mixed mullerian tumors of the uterus. One hundred nineteen pathologically confirmed uterine cancer samples were studied (66 endometrioid, 24 papillary serous, and 29 mixed mullerian tumors). Gene expressions were analyzed using the Affymetrix Human Genome Arrays U133A and U133B Genechip set. Unsupervised analysis revealed distinct global gene expression patterns of endometrioid, papillary serous, mixed mullerian tumors, and normal tissues as grossly separated clusters. Two-sample t tests comparing endometrioid and papillary serous, endometrioid and mixed mullerian tumor, and papillary serous and mixed mullerian tumor pairs identified 1,055, 5,212, and 1,208 differentially expressed genes at P < 0.001, respectively. These data revealed that distinct patterns of gene expression characterize various histologic types of uterine cancer. Gene expression profiles for select genes were confirmed using quantitative PCR. An understanding of the molecular heterogeneity of various histologic types of endometrial cancer has the potential to lead to better individualization of treatment in the future.
Relationship of Pulmonary Artery-Wedge Pressure to Left Atrial Pressure in Man
Authors: Peter C. Luchsinger, Harry W. Seipp, Dali J. Patel
Journal: Circulation Research (1962)

The pulmonary artery-wedge and left atrial pressures were recorded simultaneously in 11 patients during a control state, during norepinephrine infusion, as well as during positive and negative intra-alveolar pressures. A good correlation (r = 0.95) found between the two pressures permits the use of corrected pulmonary artery-wedge pressure in calculation of pulmonary vascular resistance under control and test conditions.
TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization
Authors: Mauricio T. Caballero, M. Elina Serra, Patricio L. Acosta, Jacqui Marzec, Luz Gibbons, Maximiliano Salim, Andrea Rodriguez, Andrea Reynaldi, Alejandro Garcia, Daniela Bado, Ursula J. Buchholz, Diego R. Hijano, Silvina Coviello, Dawn Newcomb, Miguel Bellabarba, Fausto M. Ferolla, Romina Libster, Ada Berenstein, Susana Siniawaski, Valeria Blumetti, Marcela Echavarria, Leonardo Pinto, Andrea Lawrence, M. Fabiana Ossorio, Arnoldo Grosman, Cecilia G. Mateu, Carola Bayle, Alejandra Dericco, Mariana Pellegrini, Ignacio Igarza, Horacio A. Repetto, Luciano Alva Grimaldi, Prathyusha Gudapati, Norberto R. Polack, Fernando Althabe, Min Shi, Fernando Ferrero, Eduardo Bergel, Renato T. Stein, R. Stokes Peebles, Mark Boothby, Steven R. Kleeberger, Fernando P. Polack
Journal: Journal of Clinical Investigation (2015)

While 30%–70% of RSV-infected infants develop bronchiolitis, 2% require hospitalization. It is not clear why disease severity differs among healthy, full-term infants; however, virus titers, inflammation, and Th2 bias are proposed explanations. While TLR4 is associated with these disease phenotypes, the role of this receptor in respiratory syncytial virus (RSV) pathogenesis is controversial. Here, we evaluated the interaction between TLR4 and environmental factors in RSV disease and defined the immune mediators associated with severe illness. Two independent populations of infants with RSV bronchiolitis revealed that the severity of RSV infection is determined by the TLR4 genotype of the individual and by environmental exposure to LPS. RSV-infected infants with severe disease exhibited a high GATA3/T-bet ratio, which manifested as a high IL-4/IFN-γ ratio in respiratory secretions. The IL-4/IFN-γ ratio present in infants with severe RSV is indicative of Th2 polarization. Murine models of RSV infection confirmed that LPS exposure, Tlr4 genotype, and Th2 polarization influence disease phenotypes. Together, the results of this study identify environmental and genetic factors that influence RSV pathogenesis and reveal that a high IL-4/IFN-γ ratio is associated with severe disease. Moreover, these molecules should be explored as potential targets for therapeutic intervention.
ISOKINETIC STRENGTH OF KNEE FLEXORS AND EXTENSORS IN VERY YOUNG SOCCER PLAYERS
Authors: Tomas Maly, Frantisek Zahalka, Lucia Mala, Jaroslav Teplan
Journal: British Journal of Sports Medicine (2013)

Background Monitoring of physical fitness characteristics in very young players could be helpful for the selection of talented youth or identification of the strengths and weaknesses in motor predispositions for physical performance. Muscular strength tested on an isokinetic dynamometer belongs to the most widely used methods of the identification of knee extensors (KE) and flexors (KF) strength in adult soccer players It appears that there is the lack of information concerning monitoring of isokinetic strength of lower limbs and its parameters in very young soccer players. The purpose of the study was to find out the level of isokinetic strength (IS) of KE and KF and to compare the selected characteristics of IS related to the movement velocity and limb dominancy in very young players. Methods Young players (n=16, age 8.8±0.4 years, body height=137.5±6.2 cm, body weight=30.7±4.1 kg) were tested on an isokinetic dynamometer Cybex Humac Norm. Maximum peak muscle torque (PT) of KE and KF, their mutual ratio (H:Q) and bilateral ratio between Q:Q or H:H were assessed during concentric contraction at different velocities (60,180,300°.s-1) in the dominant leg (DL) and non-dominant leg (NL). Mixed-design ANOVA was used for evaluation of PT differences between the factors (angular velocity, limb dominancy, muscle groups–KE, KF). For multiple comparisons we used Bonferonni's post-hoc test. Statistical significance was set at p≤0.05. Effect size was assessed using the ηp2 coefficient. Results The results of PT during 60,180 and 300°.s-1 were (KE [DL]: 60.9±11.6, 39.2±7.3, 30.9±5.4 N•m, [NL]: 60.8±12.2, 41.1±7.8, 33.6±6.3 N•m and for KF [DL]: 34.5±6.2, 24.5±4.1, 19.7±4.3 N•m, [NL]: 33.2±5.7, 24.6±5.8, 20.0±4.8 N•m). Movement velocity had a significant effect on the level of PT (peak torque) in the players F(1.3, 77.9)=414.9, p&lt;0.01, ηp2=0.874 and HQ ratio (F(1.7, 49.8)=7.6, p&lt;0.01, ηp2=0.202. With increasing velocity, significant differences were revealed in PT (L vs M, L vs H, M vs. H p&lt;0.01) and HQ ratio (L vs M, L vs H p &lt;0.05). Limb dominancy did not significantly influence the level of PT F(1, 60)=0.180, p&gt;0.05, ηp2=0.687 or H:Q F(1, 30)=0.760, p&gt;0.05, ηp2=0.025. Movement velocity and limb dominancy did not have any significant effect on the bilateral ratio between QQ and HH in young soccer players (p&gt;0.05). Conclusion The results indicated significant differences in PT and HQ in relation to movement velocity. On the contrary, no significant differences were found in bilateral ratio (Q:Q, H:Q). Limb dominancy did not significantly affect any of the observed characteristics. The presented data may contribute to comparison or establishment of standards for strength profile in this age category. Supported by GAČR P407/11/ P704 and MSM 0021620864.
Renal impairment after spontaneous bacterial peritonitis in cirrhosis: Incidence, clinical course, predictive factors and prognosis
Authors: Antonio Follo, Jose María Llovet, Miquel Navasa, Ramón Planas, Xavier Forns, Anna Francitorra, Antoni Rimola, Miguel Angel Gassull, Vicente Arroyo, Joan Rodés
Journal: Hepatology (1994)

Although spontaneous bacterial peritonitis is considered a precipitating factor of renal impairment in cirrhosis, no study specifically addressing this problem has been reported. This study was aimed at assessing the incidence, clinical course, predictive factors and prognosis of renal impairment in cirrhotic patients with peritonitis. Therefore, 252 consecutive episodes of spontaneous bacterial peritonitis in 197 patients were analyzed. Clinical and laboratory data obtained before and after diagnosis of peritonitis were considered as possible predictors of renal impairment and hospital mortality. Renal impairment occurred in 83 (33%) episodes, and in every instance it fulfilled the criteria of functional kidney failure. Renal impairment was progressive in 35 episodes, steady in 27 and transient in 21. Blood urea nitrogen and serum sodium concentration before peritonitis and band neutrophils count in blood at diagnosis were independent predictors for the development of renal impairment. Renal impairment was the strongest independent predictor of mortality during hospitalization. Other independent prognostic factors were blood urea nitrogen level before peritonitis, age, positive ascitic fluid culture and serum bilirubin level during infection. These results indicate that renal impairment is a frequent event in cirrhotic patients with spontaneous bacterial peritonitis that occurs mainly in patients with kidney failure before infection. Renal impairment is the most important predictor of hospital mortality in cirrhotic patients with spontaneous bacterial peritonitis. (Hepatology 1994;20:1495-1501).
Double-blind, randomised, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy
Authors: M. Aapro, A. Fabi, F. Nolè, M. Medici, G. Steger, C. Bachmann, S. Roncoroni, F. Roila
Journal: Annals of Oncology (2010)

Background: To reduce side-effects of corticosteroid-containing antiemetic regimens, tailoring antiemetic schedules to specific requirements of different patients could be of benefit. We evaluated the possibility to reduce the total dose of corticosteroids when palonosetron, a long-acting second-generation 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, is used.Materials and methods: Double-blind, multicentre, noninferiority study of chemotherapy-naive breast cancer patients receiving 0.25 mg palonosetron and 8 mg dexamethasone on day 1, randomly assigned to receive placebo (n = 151) or 4 mg b.i.d. dexamethasone (n = 149) on days 2 and 3. Primary end point was complete response (CR) rate (no emesis, no rescue medication) in the overall (days 1–5) period. Secondary end points were CR rates in the acute (day 1) and delayed (days 2–5) periods, rates of no emesis and no nausea and impact on daily functioning (Functional Living Index-Emesis).Results: Noninferiority between the two treatments was demonstrated by similar CR rates (P = 0.487) in the overall period. Most parameters showed that palonosetron and dexamethasone on day 1 only offer chemotherapy-induced nausea and vomiting protection similar to multiple-day dexamethasone administration.Conclusion: In patients treated with a single injection of palonosetron on day 1, reducing dexamethasone is an option that is not associated with significant reduction in antiemetic control during the 5-day period or an impact on patient functioning.
Treatment and Adequacy of Treatment of Mental Disorders Among Respondents to the Mexico National Comorbidity Survey
Authors: Guilherme Borges, Maria Elena Medina-Mora, Philip S Wang, Carmen Lara, Patricia Berglund, Ellen Walters
Journal: American Journal of Psychiatry (2006)

Objective: This study described the rate and adequacy of mental health service use among participants in the Mexico National Comorbidity Survey and the correlates of any 12-month treatment and of adequate treatment. Method: The authors conducted face-to-face household surveys of a probability sample of individuals ages 18 to 65 years in the noninstitutionalized population living in urban areas of Mexico from 2001 to 2002. The use of mental health services and 12-month DSM-IV disorders was assessed with the World Mental Health version of the World Health Organization Composite International Diagnostic Interview. The rates and correlates of any service use and the adequacy of treatment were identified in logistic regression analyses, taking into account the complex sample design and weighting process. Results: The data reported here were based on 2,362 interviews. Fewer than one in five respondents with any psychiatric disorder during the last 12 months used any service during the prior year. The rates of service use by those with mood disorders were somewhat higher. About one in every two respondents who used services received minimally adequate care. Conclusions: The authors found large unmet needs for mental health services among those with psychiatric disorders. Those with mental illness and those who deliver or seek to improve mental health care in Mexico face enormous challenges.
Early exercise training after myocardial infarction prevents contractile but not electrical remodelling or hypertrophy
Authors: V. Bito, M. C. de Waard, L. Biesmans, I. Lenaerts, S. Ozdemir, E. van Deel, Y. Abdel-Mottaleb, R. Driesen, P. Holemans, D. J. Duncker, K. R. Sipido
Journal: Cardiovascular Research (2009)

AimsExercise started early after myocardial infarction (MI) improves in vivo cardiac function and myofilament responsiveness to Ca2+. We investigated whether this represents partial or complete reversal of cellular remodelling.