tbuckley/cabot-search huggingface dataset:
Pulse Versus Daily Oral Cyclophosphamide for Induction of Remission in Antineutrophil Cytoplasmic Antibody—Associated Vasculitis
Authors: Kirsten de Groot
Journal: Annals of Internal Medicine (2009)

Background: Current therapies for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis are limited by toxicity. Objective: To compare pulse cyclophosphamide with daily oral cyclophosphamide for induction of remission. Design: Randomized, controlled trial. Random assignments were computer-generated; allocation was concealed by faxing centralized treatment assignment to providers at the time of enrollment. Patients, investigators, and assessors of outcomes were not blinded to assignment. Setting: 42 centers in 12 European countries. Patients: 149 patients who had newly diagnosed generalized ANCA-associated vasculitis with renal involvement but not immediately life-threatening disease. Intervention: Pulse cyclophosphamide, 15 mg/kg every 2 to 3 weeks (76 patients), or daily oral cyclophosphamide, 2 mg/kg per day (73 patients), plus prednisolone. Measurement: Time to remission (primary outcome); change in renal function, adverse events, and cumulative dose of cyclophosphamide (secondary outcomes). Results: Groups did not differ in time to remission (hazard ratio, 1.098 [95% CI, 0.78 to 1.55]; P = 0.59) or proportion of patients who achieved remission at 9 months (88.1% vs. 87.7%). Thirteen patients in the pulse group and 6 in the daily oral group achieved remission by 9 months and subsequently had relapse. Absolute cumulative cyclophosphamide dose in the daily oral group was greater than that in the pulse group (15.9 g [interquartile range, 11 to 22.5 g] vs. 8.2 g [interquartile range, 5.95 to 10.55 g]; P < 0.001). The pulse group had a lower rate of leukopenia (hazard ratio, 0.41 [CI, 0.23 to 0.71]). Limitations: The study was not powered to detect a difference in relapse rates between the 2 groups. Duration of follow-up was limited. Conclusion: The pulse cyclophosphamide regimen induced remission of ANCA-associated vasculitis as well as the daily oral regimen at a reduced cumulative cyclophosphamide dose and caused fewer cases of leukopenia. Primary Funding Source: The European Union.
Cardiovascular stress on an elite basketball referee during national competition: Table 1
Authors: A S Leicht
Journal: British Journal of Sports Medicine (2004)

This case report examined the cardiovascular stress imposed on an experienced elite basketball referee during national competition. The average heart rate was similar for all matches, approximated 73% of maximum heart rate, and was experienced for most (>63%) of the match. Similar relative exercise intensity was demonstrated regardless of match play (men's v women's) and officiating type (two v three-referee). Further study is needed to document the physiological characteristics of elite basketball referees for greater performance.
The Small Pulmonary Arteries of the Llama and Other Domestic Animals Native to High Altitudes
Authors: D. Heath, Y. Castillo, J. Arias-Stella, P. Harris
Journal: Cardiovascular Research (1969)

Journal Article The Small Pulmonary Arteries of the Llama and Other Domestic Animals Native to High Altitudes Get access D. Heath, D. Heath From the Departments of Pathology and Medicine, University of Birmingham, England, and the High Altitudes Research Institute, Peruvian University of Medical and Biological Sciences, Lima, Peru Search for other works by this author on: Oxford Academic PubMed Google Scholar Y. Castillo, Y. Castillo From the Departments of Pathology and Medicine, University of Birmingham, England, and the High Altitudes Research Institute, Peruvian University of Medical and Biological Sciences, Lima, Peru Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Arias-Stella, J. Arias-Stella From the Departments of Pathology and Medicine, University of Birmingham, England, and the High Altitudes Research Institute, Peruvian University of Medical and Biological Sciences, Lima, Peru Search for other works by this author on: Oxford Academic PubMed Google Scholar P. Harris P. Harris From the Departments of Pathology and Medicine, University of Birmingham, England, and the High Altitudes Research Institute, Peruvian University of Medical and Biological Sciences, Lima, Peru Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 3, Issue 1, January 1969, Pages 75–78, https://doi.org/10.1093/cvr/3.1.75 Published: 01 January 1969 Article history Received: 20 November 1966 Published: 01 January 1969
Hold Me Tight
Authors: Monte S. Willis, Cam Patterson
Journal: Circulation (2010)

][3][4] Although the compensatory increases in chaperones/cochaperones work to prevent misfolding, refold denatured proteins, and/or target them for degradation, this system can become overwhelmed, leading to worsening of cardiac function.In fact, recent studies have demonstrated experimentally that increasing the burden of misfolded proteins in the heart can contribute to the development of cardiac dysfunction. 5In this review, we discuss the role of heat shock proteins (HSPs) in common cardiac diseases, including cardiac hypertrophy, heart failure, and ischemia/reperfusion injury.Furthermore, we delineate the many specific mechanisms by which these chaperones, cochaperones, and heat shock factor (HSF) transcription factors have been found to be cardioprotective in experimental models.Lastly, we review recent studies involving drugs that are being developed (and currently used) to increase the expression (and presumably function) of chaperone/cochaperone systems that may be applicable to the treatment of common cardiac diseases and familial cardiac diseases with a pathogenesis that includes a major component of misfolded proteins (eg, desminopathies).
A multicentre study of loratadine, clemastine and placebo in patients with perennial allergic rhinitis
Authors: L. Frøulund, B. Etholm, K. Irander, T. A. Johannessen, L. ÖDkvist, B. Ohlander, B. Weeke
Journal: Allergy (1990)

This multicentre, double-blind, randomized parallel-group study compared 3 weeks' treatment with either loratadine (Clarityn) 10 mg once daily, or clemastine (Tavegyl) 1 mg twice daily, and placebo in outpatients with active perennial allergic rhinitis. 155 patients were evaluated for efficacy and safety. Grading of four nasal and three non-nasal symptoms, rhinoscopy signs, and therapeutic response was performed on treatment days 6, 13, and 20. Patients recorded daily symptoms and possible adverse experiences in a diary, also indicating when symptoms of active rhinitis were relieved. Loratadine and clemastine were statistically significantly superior to placebo throughout the study (P less than 0.05), based on assessment of patients' nasal and eye symptoms, patients' diary scores, rhinoscopy signs of symptoms, and onset of relief. The loratadine group showed a statistically significantly (P less than 0.05) faster onset of relief of symptoms compared with the group treated with clemastine. Concerning nasal stuffiness, loratadine was significantly (P less than 0.05) superior to clemastine after 1 week's treatment. Reports of adverse reactions showed that significantly (P less than 0.05) more patients complained of sedation in the clemastine than in the loratadine group. Regarding other adverse experiences and laboratory tests, the three treatment groups were statistically comparable (P less than 0.05). The study showed that compared with placebo both loratadine and clemastine were effective in relieving nasal and eye symptoms in patients with perennial allergic rhinitis. Loratadine was safe and well tolerated and was significantly less sedative than clemastine; loratadine may therefore possess an advantage in clinical use in the treatment of perennial allergic rhinitis.
Matrix metalloproteinase-2 regulates vascular patterning and growth affecting tumor cell survival and invasion in GBM
Authors: Rose Du, Claudia Petritsch, Kan Lu, Patty Liu, Anna Haller, Ruth Ganss, Hanqiu Song, Scott Vandenberg, Gabriele Bergers
Journal: Neuro-Oncology (2008)

Glioblastoma multiforme (GBM) is one the most aggressive brain tumors due to the fast and invasive growth that is partly supported by the presence of extensive neovascularization. The matrix metalloproteinase MMP-2 has been associated with invasive and angiogenic properties in gliomas and is a marker of poor prognosis. Since MMP-2 is expressed in both tumor cells and endothelial cells in GBM, we generated genetically engineered MMP-2 knockout (MMP-2ko) GBM to examine the importance of the spatial expression of MMP-2 in tumor and/or normal host-derived cells. MMP-2–dependent effects appeared to be dose-dependent irrespective of its expression pattern. GBM completely devoid of MMP-2 exhibited markedly increased vascular density associated with vascular endothelial growth factor receptor 2 (VEGFR2) activation and enhanced vascular branching and sprouting. Surprisingly, despite the high vascular density, tumor cells were more prone to apoptosis, which led to prolonged survival of tumor-bearing mice, suggesting that the increased vascularity is not functional. Congruently, tumor vessels were poorly perfused, exhibited lower levels of VEGFR2, and did not undergo proper maturation because pericytes of MMP-2ko tumors were not activated and were less abundant. As a result of impaired and dysfunctional angiogenesis, MMP-2ko GBM became more invasive, predominantly by migrating along blood vessels into the brain parenchyma.
Effectiveness of Fundoplication at the Time of Gastrostomy in Infants With Neurological Impairment
Authors: Douglas C. Barnhart, Matthew Hall, Sanjay Mahant, Adam B. Goldin, Jay G. Berry, Roger G. Faix, J. Michael Dean, Rajendu Srivastava
Journal: JAMA Pediatrics (2013)

Gastrostomy tube (GT) placement is the most common gastrointestinal operation performed on neonates. Concomitant fundoplication is used variably to prevent complications of gastroesophageal reflux, but its effectiveness is unproven.To compare the effect of fundoplication at the time of GT placement vs GT placement alone on subsequent reflux-related hospitalizations in infants with neurological impairment.Retrospective, observational cohort study, defined by birth between January 1, 2005, and December 31, 2010, at 42 children's hospitals in the United States, with a 1-year follow-up period among 4163 infants with neurological impairment who underwent GT placement with or without fundoplication during their neonatal intensive care unit stay.Fundoplication and GT placement vs. GT placement alone.One-year postprocedural reflux-related hospitalization rates, defined as hospitalization for asthma, mechanical ventilation, gastroesophageal reflux disease, and aspiration or other types of pneumonia. Propensity to undergo concomitant fundoplication was modeled using demographics, prior procedures (tracheostomy and mechanical ventilation), and prior diagnoses (eg, pneumonia, gastroesophageal reflux disease, and other comorbidities).Overall, 4163 of 42,796 infants (9.7%) with neurological impairment admitted to the neonatal intensive care unit underwent GT placement alone or with fundoplication. Infants who concomitantly underwent fundoplication had more reflux-related hospitalizations during the first year than those who underwent GT placement alone (mean, 1.02; 95% CI, 0.93-1.10 vs mean, 0.92; 95% CI, 0.91-1.00). Of 1404 infants who underwent fundoplication, 1027 (73.1%) were matched based on propensity scores. The mean difference of the matched cohort for any reflux-related hospitalizations was -0.05 (95% CI, -0.20 to 0.15) per year.Infants with neurological impairment who underwent fundoplication at the time of GT placement did not have a reduced rate of reflux-related hospitalizations during the first year compared with those who underwent GT placement alone, despite propensity score matching. This may be due to a lack of effectiveness of fundoplication in preventing these complications or due to differences in the patient groups that were inadequately accounted for in the matching.
Temporal Patterns of Antihypertensive Medication Use Among Older Adults, 1989 Through 1992
Authors: Bruce M. Psaty
Journal: JAMA (1995)

To describe the changing patterns of antihypertensive medication use in the years immediately before and after the publication of the results of three major clinical trials of the treatment of hypertension in older adults.In this cohort study, adults 65 years or older were examined annually on four occasions between June 1989 and May 1992, and the use of antihypertensive medications was assessed by inventory at each visit. The four visits defined the boundaries of three study periods. For each study period, participants receiving antihypertensive therapy were either continuous users (n = 1667, 1643, and 1605, respectively) or starters (n = 157, 142, 120) of hypertensive therapy. The large clinical trials that convincingly proved the efficacy and safety of low-dose diuretic therapy in older adults were published during the latter parts of period 2 and the early parts of period 3.Among starters, the proportion initiating therapy on diuretics increased from 35.9% in period 2 to 47.5% in period 3, significantly so among women (P = .04). The proportions initiating other drugs displayed no significant trends. Among continuous users, the use of diuretics, beta-blockers, and vasodilators generally decreased over the 3-year period, while the use of calcium channel blockers and angiotensin-converting enzyme inhibitors increased significantly in each of the three periods (P < .05). The decline of 2.7% in the prevalence of diuretic use in period 1 abated during period 2 (1.8% decline), and it slowed significantly (P = .03) to almost a complete halt during period 3 (0.2% decline). The rate of increase in the use of calcium channel blockers slowed significantly (P = .01) between period 1 (+6.7%) and period 3 (+2.8%).Although other factors such as cost may have been important, the temporal trends in antihypertensive drug therapy coincided in time with and may have reflected in part the influence of the major clinical trials on the patterns of clinical practice.
Ultrasound guided injection of plantar fasciitis
Authors: M. QUINN, A. GOUGH;, D. KANE, O. FITZGERALD
Journal: Annals of the Rheumatic Diseases (1998)

Kane and colleagues rightly emphasise the increasing importance of diagnostic ultrasound in rheumatological practice.1 New equipment with small transducers and greatly magnified images, albeit more expensive, make the case for its routine use in clinics stronger all the time. As Kane points out, plantar fasciitis is an excellent example of this, both for diagnosis and ensuring correct placement of injection therapy. We entirely agree that it is altogether better than using bone scintigraphy in this condition.

As Kane et al suggest, plantar fasciitis can be difficult to treat. They claim that clinical results are improved by using an ultrasound guided injection. Even accounting for the sample size, their results are difficult to interpret. For the majority of patients appropriate advice on footwear, weight reduction, stretching exercises, non-steroidal anti-inflammatory drugs, and insoles are …
Temsirolimus in Daily Use: Results of a Prospective Multicentre Noninterventional Study of Patients with Metastatic Kidney Cancer
Authors: Andres Jan Schrader, Sandra Seseke, Christian Keil, Edwin Herrmann, Peter J. Goebell, Steffen Weikert, Sandra Steffens, Lothar Bergmann, Jan Roigas, Thomas Steiner
Journal: European Urology (2013)
Critical Role for Leukocyte Hypoxia Inducible Factor-1α Expression in Post-Myocardial Infarction Left Ventricular Remodeling
Authors: Feng Dong, Mazen Khalil, Matt Kiedrowski, Caitlin O'Connor, Erin Petrovic, Xiaorong Zhou, Marc S. Penn
Journal: Circulation Research (2009)

Hypoxia inducible factor (HIF)-1alpha is a transcription factor stabilized by hypoxia. It regulates cytokines involved in the inflammatory response after ischemia and affects white blood cell (WBCs) function. The effect of HIF-1alpha on WBC function and inflammation following myocardial infarction (MI) is unknown.We assessed peritoneal and myocardial inflammation in the setting of low WBC HIF-1alpha expression through bone marrow transplantation of hematopoietic stem cells transfected with scramble or HIF-1alpha small interfering (si)RNA.Rosa hematopoietic stem cells (lin(-), cKit(+)) were transfected with a green fluorescent protein (GFP) reporter lentivirus encoding a siRNA to HIF-1alpha or scramble. Irradiated 6- to 8-week-old C57/BL6J mice received 50 000 GFP(+) HIF-1alpha or scramble siRNA-transfected hematopoietic stem cells. Peritonitis or myocardial infarction via left anterior descending coronary artery ligation was induced 6 weeks after bone marrow transplantation. In the peritonitis model, HIF-1alpha siRNA group exhibited a significant decrease in neutrophil and monocyte entry to the peritoneum compared to scramble mice. Similarly neutrophil infiltration into the infarct zone was decreased in the HIF-1alpha siRNA group. No difference of myocardial infarct size was observed between groups. Interestingly, the ejection fraction were similar in both groups at baseline and 3 days post-MI but increased significantly in the HIF-1alpha siRNA group compared to control beginning 7 days after MI. Gene array studies demonstrated that downregulation of WBC HIF-1alpha was associated with decreased WBC CCR1, -2, and -4 expression. Chemotaxis assay results confirmed that decreased monocyte migration induced by downregulation of HIF-1alpha was partially reversed by overexpression of CCR2.Downregulation of leukocyte HIF-1alpha expression resulted in decreased recruitment of WBC to the sites of inflammation and improvement in cardiac function following MI. Downregulation of HIF-1alpha suppressed WBC cytokine receptors CCR1, -2, and -4, which are necessary for WBC mobilization and recruitment to inflammatory cytokines following MI. The effects of downregulation of leukocyte HIF-1alpha on WBC migration are attributable, at least in part, to the decreased CCR2 expression. These results demonstrate that WBC infiltration into the newly injured myocardium plays a significant role in left ventricular remodeling, but not infarct size.
Unique DNA Methylation Patterns Distinguish Noninvasive and Invasive Urothelial Cancers and Establish an Epigenetic Field Defect in Premalignant Tissue
Authors: Erika M. Wolff, Yoshitomo Chihara, Fei Pan, Daniel J. Weisenberger, Kimberly D. Siegmund, Kokichi Sugano, Kiyotaka Kawashima, Peter W. Laird, Peter A. Jones, Gangning Liang
Journal: Cancer Research (2010)

Abstract Urothelial cancer (UC) develops along two different genetic pathways, resulting in noninvasive or invasive tumors. However, it is unknown whether there are also different epigenetic pathways in UC. UC is also characterized by a high rate of recurrence, and the presence of a field defect has been postulated. In this study, we compared the DNA methylation patterns between noninvasive and invasive UC and the DNA methylation patterns between normal-appearing urothelium from bladders with cancer and urothelium from cancer-free bladders. We used the Illumina GoldenGate methylation assay at 1,370 loci in 49 noninvasive urothelial tumors, 38 invasive tumors with matched normal-appearing urothelium, and urothelium from 12 age-matched UC-free patients. We found distinct patterns of hypomethylation in the noninvasive tumors and widespread hypermethylation in the invasive tumors, confirming that the two pathways differ epigenetically in addition to genetically. We also found that 12% of the loci were hypermethylated in apparently normal urothelium from bladders with cancer, indicating an epigenetic field defect. X-chromosome inactivation analysis indicated that this field defect did not result in clonal expansion but occurred independently across the urothelium of bladders with cancer. The hypomethylation present in noninvasive tumors may counterintuitively provide a biological explanation for the failure of these tumors to become invasive. In addition, an epithelium-wide epigenetic defect in bladders with cancer might contribute to a loss of epithelial integrity and create a permissible environment for tumors to arise. Cancer Res; 70(20); 8169–78. ©2010 AACR.
A FURTHER CONTRIBUTION TO VITAMIN C THERAPY IN EXPERIMENTAL POLIOMYELITIS
Authors: C. W. Jungeblut
Journal: The Journal of Experimental Medicine (1939)

1. Multiple paralytic doses of poliomyelitis virus (RMV strain), when brought together with small amounts of synthetic ascorbic acid in vitro, are rendered non-infectious as determined by intracerebral injection of such mixtures into rhesus monkeys. 2. Vitamin C administration to monkeys infected intranasally with the RMV strain produces results which differ in accordance with the technique employed for nasal instillation. With an infection of maximum severity, induced by flooding the nasal portal of entry with large amounts of virus, vitamin C administration fails to exert any demonstrable influence on the course of the disease. With a less forceful method of droplet instillation, the picture of the disease in control animals becomes so variable that the results cannot be easily interpreted; but the available data suggest that vitamin C treatment may be a factor in converting abortive attacks into an altogether non-paralytic infection. 3. The administration of synthetic vitamin C to monkeys infected intracerebrally with small doses of the RMV strain gives results comparable to those previously obtained with this substance in monkeys infected intracerebrally with the Aycock strain of poliomyelitis virus. 4. The implications of the findings are discussed.
Polymorphisms in 17q12-21 are associated with asthma exacerbation and lung function in asthmatic children
Authors: Mario Blekic, Blazenka Kljaic Bukvic, Neda Aberle, Susana Marinho, Adnan Custovic, Angela Simpson
Journal: European Respiratory Journal (2011)

Background:  More then 15 studies associated genetic variants in 17q21 region with asthma. We aimed to investigate whether amongst Croatian asthmatic children, genetic variants in this region are associated with asthma severity and exacerbation.   Methods:  We recruited 423 children aged 6-18 years with physician-diagnosed asthma. Information on hospital admission with asthma exacerbations was retrieved from medical records. Data on wheeze frequency and environmental tobacco smoke (ETS) exposure was collected using validated questionnaire. Lung function (FEV 1 %predicted) was measured using spirometry. We analyzed 35 haplotype-tagging SNPs in 17q21.   Results:  We found significant associations between 4 SNPs and hospital admissions (rs12150079, rs7212938, rs2290400, rs8067378). For example, G allele homozygotes in rs12150079 were at higher risk of being admitted to hospital than carriers of A allele (aOR 1.85, 95%CI 1.26-2.72, p=0.002); this SNP was also associated with current wheezing. Six SNPs were associated with lung function (rs9635726, rs921651, rs9900538, rs3169572, rs4795403, rs471692). In addition, we observed significant interaction between 3 SNPs (rs12603332, rs8067378, rs9303277) and  in utero  ETS exposure in relation to lung function (p int  1 %predicted than minor allele carriers, but amongst non-exposed children there was no difference in lung function between different genotype groups.   Conclusion:  Variants in 17q12-21 region may be associated with asthma severity and may interact with  in utero  ETS exposure in determining lung function amongst asthmatic children.