tbuckley/cabot-search huggingface dataset:
Second by second patterns in cortical electroencephalograph and systolic blood pressure during Cheyne-Stokes
Authors: R.J.O. Davies, L.S. Bennet, C Barbour, L Tarassenko, J.R. Stradling
Journal: European Respiratory Journal (1999)

Little is known about how arousal develops during the ventilatory phase of Cheyne-Stokes breathing. This study employs neural network analysis of electroencephalograms (EEGs) to describe these changes and relate them to changes in systolic blood pressure, which is probably a subcortical marker of arousal. Six patients with Cheyne-Stokes respiration (apnoea/hypopnoea index 32-69 h(-1)) caused by stable chronic heart failure underwent polysomnography including arterial beat-to-beat systolic blood pressure determination. Periods of 15 sequential apnoeas during nonrapid eye movement sleep were identified for each subject. For each apnoea, the EEG was examined second-by-second using neural net analysis from 28 s before to 28 s after apnoea termination (first return of oronasal airflow), and this was compared with the systolic blood pressure pattern. During the apnoeic phase, sleep deepened progressively. Arousal started to develop at or just before apnoea termination and progresses through the breathing phase. The rise and fall in the systolic blood pressure closely followed the rise and fall in electroencephalographic sleep depth. In conclusion, during Cheyne-Stokes breathing, cortical electroencephalographic arousal begins at or just before the resumption of breathing. Cortical electroencephalographic sleep depth changes are closely mirrored by changes in arterial systolic blood pressure, suggesting that the state changes in the cortical and basal brain structures may be synchronous.
Gene Targeting Approaches to Analyzing Hypertension
Authors: NOBUYUKI TAKAHASHI, OLIVER SMITHIES
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Essential hypertension probably results from combinations of small genetic variations that are partly normal variations and may not be appreciably harmful individually. Strategies to identify genes contributing to hypertension are discussed in this review. Gene targeting approaches, especially gene titration, have been used in these studies of hypertension. Gene titration experiments vary the expression of a chosen gene product by generating animals having different numbers of copies of the gene coding for the product. Gene titration is powerful for analyzing quantitative variations seen in common polygenic disorders, such as kidney diseases, diabetes mellitus, and atherosclerosis, as well as hypertension, because it allows tests of causation by determining the effects on a phenotype by changes in expression of the altered gene and because it matches normal quantitative variations more closely than is possible with classic transgenic mice. The use of zero-copy (gene “knockout”) animals generated by gene disruption for studies of qualitative gene effects is also discussed. These various gene targeting experiments help identify genes regulating BP, promote a better understanding of the pathophysiology of the condition, and help identify potential targets for therapies.
Cellular localization and regional distribution of an angiotensin II-forming chymase in the heart.
Authors: H Urata, K D Boehm, A Philip, A Kinoshita, J Gabrovsek, F M Bumpus, A Husain
Journal: Journal of Clinical Investigation (1993)

The human heart is a target organ for the octapeptide hormone, angiotensin II (Ang II). Recent studies suggest that the human heart contains a dual pathway of Ang II formation in which the major Ang II-forming enzymes are angiotensin I-converting enzyme (ACE) and chymase. Human heart chymase has recently been purified and its cDNA and gene cloned. This cardiac serine proteinase is the most efficient and specific Ang II-forming enzyme described. To obtain insights into the cardiac sites of chymase-dependent Ang II formation, we examined the cellular localization and regional distribution of chymase in the human heart. Electron microscope immunocytochemistry using an anti-human chymase antibody showed the presence of chymase-like immunoreactivity in the cardiac interstitium and in cytosolic granules of mast cells, endothelial cells, and some mesenchymal interstitial cells. In the cardiac interstitium, chymase-like immunoreactivity is associated with the extracellular matrix. In situ hybridization studies further indicated that chymase mRNA is expressed in endothelial cells and in interstitial cells, including mast cells. Tissue chymase levels were determined by activity assays and by Western blot analyses. Chymase levels were approximately twofold higher in ventricles than in atria. There were no significant differences in chymase levels in ventricular tissues obtained from non-failing donor hearts, failing ischemic hearts, or hearts from patients with ischemic cardiomyopathy. These findings suggest that a major site of chymase-dependent Ang II formation in the heart is the interstitium and that cardiac mast cells, mesenchymal interstitial cells, and endothelial cells are the cellular sites of synthesis and storage of chymase. In the human heart, because ACE levels are highest in the atria and chymase levels are highest in ventricles, it is likely that the relative contribution of ACE and chymase to cardiac Ang II formation varies with the cardiac chamber. Such differences may lead to differential suppression of cardiac Ang II levels during chronic ACE inhibitor therapy in patients with congestive heart failure.
Chronic Severe Hemolytic Anemia Related to Surreptitious Phenazopyridine Abuse
Authors: Robert J. Thomas
Journal: Annals of Internal Medicine (1994)

Letters15 August 1994Chronic Severe Hemolytic Anemia Related to Surreptitious Phenazopyridine AbuseRobert J. Thomas, MD, Sudarshan Doddabele, MD, and Anand B. Karnad, MDRobert J. Thomas, MDSearch for more papers by this author, Sudarshan Doddabele, MDSearch for more papers by this author, and Anand B. Karnad, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-4-199408150-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:A 43-year-old white woman with a history of chronic pancreatitis, diabetes, anxiety, recurrent urinary tract infections, and chronic lower-back and pelvic pain was noted to have normocytic anemia (hemoglobin concentration, 9 to 10 g/dL) since 1987. Serum iron, vitamin B (12), and folate levels were normal.Macrocytic anemia with 20% to 30% reticulocytes and a peripheral smear consistent with intravascular hemolysis (Figure 1) were first noted in October 1991. Heinz body preparations and urine hemosiderin results were positive. Diagnostic evaluations for erythrocyte enzyme deficiencies, Wilson disease, autoimmune hemolytic anemias, heavy metal toxicity, and paroxysmal nocturnal hemoglobinuria were ...References1. Gavish D, Knobler H, Gottehrer N, Israeli A, Kleinman Y. Methemoglobinemia, muscle damage and renal failure complicating phenazopyridine overdose. Isr J Med Sci. 1986; 22:45-7. Google Scholar2. Hood JW, Toth WN. Jaundice caused by phenazopyridine hydrochloride. JAMA. 1966; 198:1366-7. Google Scholar3. Eybel CE, Armbruster KF, Ing TS. Skin pigmentation and acute renal failure in a patient receiving phenazopyridine therapy. JAMA. 1974; 228:1027-8. Google Scholar Author, Article, and Disclosure InformationAuthors: Robert J. Thomas, MD; Sudarshan Doddabele, MD; Anand B. Karnad, MD PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe Effect of Preoperative Phenazopyridine on Urinary Retention Following Midurethral SlingPhenazopyridineUrinary tract analgesics for the treatment of patients with acute cystitis: where is the clinical evidence?An Over-the-counter OmissionPhenazopyridine abuse 15 August 1994Volume 121, Issue 4 Page: 308 Keywords Attention Drugs Hemoglobin Hemolytic anemia Syncope Systolic ejection murmur Toxicity Ulcers Urine ePublished: 15 August 2000 Issue Published: 15 August 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Serum 25-Hydroxyvitamin D Concentrations and Risk for Hip Fractures
Authors: Jane A. Cauley
Journal: Annals of Internal Medicine (2008)

Background: The relationship between serum 25-hydroxyvitamin D [25(OH) vitamin D] concentration and hip fractures is unclear. Objective: To see whether low serum 25(OH) vitamin D concentrations are associated with hip fractures in community-dwelling women. Design: Nested case–control study. Setting: 40 clinical centers in the United States. Participants: 400 case-patients with incident hip fracture and 400 control participants matched on the basis of age, race or ethnicity, and date of blood draw. Both groups were selected from 39 795 postmenopausal women who were not using estrogens or other bone-active therapies and who had not had a previous hip fracture. Measurements: Serum 25(OH) vitamin D was measured and patients were followed for a median of 7.1 years (range, 0.7 to 9.3 years) to assess fractures. Results: Mean serum 25(OH) vitamin D concentrations were lower in case-patients than in control participants (55.95 nmol/L [SD, 20.28] vs. 59.60 nmol/L [SD, 18.05]; P = 0.007), and lower serum 25(OH) vitamin D concentrations increased hip fracture risk (adjusted odds ratio for each 25-nmol/L decrease, 1.33 [95% CI, 1.06 to 1.68]). Women with the lowest 25(OH) vitamin D concentrations (≤47.5 nmol/L) had a higher fracture risk than did those with the highest concentrations (≥70.7 nmol/L) (adjusted odds ratio, 1.71 [CI, 1.05 to 2.79]), and the risk increased statistically significantly across quartiles of serum 25(OH) vitamin D concentration (P for trend = 0.016). This association was independent of number of falls, physical function, frailty, renal function, and sex-steroid hormone levels and seemed to be partially mediated by bone resorption. Limitations: Few case-patients were nonwhite women. Bone mineral density and parathyroid hormone levels were not accounted for in the analysis. Conclusion: Low serum 25(OH) vitamin D concentrations are associated with a higher risk for hip fracture.
Screening for Down's syndrome: effects, safety, and cost effectiveness of first and second trimester strategies Commentary: Results may not be widely applicable Authors' response
Authors: R E Gilbert, C Augood, R Gupta, A E Ades, S Logan, M Sculpher, J H P van der Meulen, E. M Wallace, S. Mulvey
Journal: BMJ (2001)

# Screening for Down's syndrome: effects, safety, and cost effectiveness of first and second trimester strategies {#article-title-2} Objective: To compare the effects, safety, and cost effectiveness of antenatal screening strategies for Down's syndrome. Design: Analysis of incremental cost effectiveness. Setting: United Kingdom. Main outcome measures: Number of liveborn babies with Down's syndrome, miscarriages due to chorionic villus sampling or amniocentesis, healthcare costs of screening programme, and additional costs and additional miscarriages per additional affected live birth prevented by adopting a more effective strategy. Results: Compared with no screening, the additional cost per additional liveborn baby with Down's syndrome prevented was £22 000 for measurement of nuchal translucency. The cost of the integrated test was £51 000 compared with measurement of nuchal translucency. All other strategies were more costly and less effective, or cost more per additional affected baby prevented. Depending on the cost of the screening test, the first trimester combined test and the quadruple test would also be cost effective options. Conclusions: The choice of screening strategy should be between the integrated test, first trimester combined test, quadruple test, or nuchal translucency measurement depending on how much service providers are willing to pay, the total budget available, and values on safety. Screening based on maternal age, the second trimester double test, and the first trimester serum test was less effective, less safe, and more costly than these four options. # Commentary: Results may not be widely applicable {#article-title-9} # Authors' response {#article-title-12}
Reduction in the adherence of Pseudomonas aeruginosa to native cystic fibrosis epithelium with anti-asialoGM1 antibody and neuraminidase inhibition
Authors: J Davies, A Dewar, A Bush, T Pitt, D Gruenert, DM Geddes, EW Alton
Journal: European Respiratory Journal (1999)

The high incidence of colonization of the cystic fibrosis (CF) airway with Pseudomonas aeruginosa has been attributed to several mechanisms including increased numbers of asialoglycolipid receptors, which may be further increased by exposure to the bacterial exoproduct, neuraminidase. This study examined whether the adherence of P. aeruginosa to fresh CF respiratory epithelial cells can be reduced in vitro by anti-asialoGM1 (anti-aGM1) antibody, neuraminidase inhibition, or the use of asialoGM1 tetrasaccharide as a competitive inhibitor. CF nasal epithelial cells were incubated with a nonmucoid strain of P. aeruginosa, in the presence or absence of a polyclonal anti-aGM1 antibody, the neuraminidase inhibitor 2,3-dehydro-2-deoxy-N-acetyl-neuraminic acid (DANA), or the tetrasaccharide moiety of aGM1. Adherence of bacteria to the apical surface of ciliated epithelial cells was quantified using scanning electron microscopy. Incubation of the cells with bacteria in the presence of either anti-aGM1 antibody or DANA significantly reduced bacterial adherence by 51(7)%, (p&lt;0.01), and 34(9)%, (p&lt;0.01), respectively. In contrast, no significant effect on P. aeruginosa binding was seen in the presence of aGM1 tetrasaccharide. The data are consistent with previous studies on cultured cells, and suggest that the in vivo effects of such interventions should be explored as potential mechanisms to reduce Pseudomonas aeruginosa colonization in cystic fibrosis.
How to isolate cardiac myocytes
Authors: J. Tytgat
Journal: Cardiovascular Research (1994)

Journal Article How to isolate cardiac myocytes Get access Jan Tytgat Jan Tytgat University of Leuven, Laboratory of Physiology, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium: Dr J Tytgat. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 2, February 1994, Pages 280–283, https://doi.org/10.1093/cvr/28.2.280 Published: 01 February 1994 Article history Received: 27 September 1993 Published: 01 February 1994
Systemic Hemodynamic and Myocardial Metabolic Effects of Isoproterenol and Angiotensin After Open-Heart Surgery
Authors: HILTRUD S. MUELLER, JOHN J. GREGORY, STANLEY GIANNELLI, STEPHEN M. AYRES
Journal: Circulation (1970)

Cardiovascular dynamics and metabolism after open heart surgery were studied in 10 patients before and after infusion of angiotensin and isoproterenol. Patients with rheumatic mitral disease showed marked lowering of cardiac index with elevation of systemic vascular resistance in the control state while those with aortic disease demonstrated less depression of cardiac index and normal resistance. The group with mitral disease also showed lower coronary blood flow and much higher coronary vascular resistance than the aortic patients. Angiotensin caused further depression of cardiac index and marked increase in pressure work. Isoproterenol augmented cardiac index but did not affect pressure work significantly. Both agents increased oxygen consumption significantly by increment in coronary flow (isoproterenol) or by widening of myocardial oxygen extraction (angiotensin). Isoproterenol is favored over angiotensin in low output states after cardiac surgery as a means of meeting oxygen demands as well as the response of cardiac index.
CA 125 half-life and CA 125 nadir during induction chemotherapy are independent predictors of epithelial ovarian cancer outcome: results of a French multicentric study
Authors: J.M. Riedinger, J. Wafflart, G. Ricolleau, N. Eche, H. Larbre, J.P. Basuyau, I. Dalifard, K. Hacene, M.F. Pichon
Journal: Annals of Oncology (2006)
Regulation of Cell Proliferation and Migration by Keratin19-Induced Nuclear Import of Early Growth Response-1 in Breast Cancer Cells
Authors: Ji-hyun Ju, Wonseok Yang, Kyung-min Lee, Sunhwa Oh, KeeSoo Nam, Sarah Shim, Soon Young Shin, Myung Chan Gye, In-Sun Chu, Incheol Shin
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Keratin19 (KRT19) is the smallest known type I intermediate filament and is used as a marker for reverse transcriptase PCR–mediated detection of disseminated tumors. In this study, we investigated the functional analysis of KRT19 in human breast cancer. Experimental Design: Using a short hairpin RNA system, we silenced KRT19 in breast cancer cells. KRT19 silencing was verified by Western blot analysis and immunocytochemistry. We further examined the effect of KRT19 silencing on breast cancer cells by cell proliferation, migration, invasion, colony formation assay, cell-cycle analysis, immunocytochemistry, immunohistochemistry, and mouse xenograft assay. Results: Silencing of KRT19 resulted in increased cell proliferation, migration, invasion, and survival. These effects were mediated by upregulation of Akt signaling as a result of reduced PTEN mRNA expression. Silencing of KRT19 decreased the nuclear import of early growth response-1 (Egr1), a transcriptional factor for PTEN transcription, through reduced association between Egr1 and importin-7. We also confirmed that silencing of KRT19 increased tumor formation in a xenograft model. Conclusions: KRT19 is a potential tumor suppressor that negatively regulates Akt signaling through modulation of Egr1 nuclear localization. Clin Cancer Res; 19(16); 4335–46. ©2013 AACR.
Phase 1 Study of MLN8237 (Alisertib) in Adult East Asian Patients (PTS) with Advanced Solid Tumors or Lymphomas
Authors: W.S. Kim, K. Venkatakrishnan, T.M. Kim, C.-C. Lin, L.S. Thye, W.J. Chng, B. Ma, M.-H. Chen, H. Liu, E. Benaim
Journal: Annals of Oncology (2013)
Systemic Inflammatory Response Syndrome Criteria in Defining Severe Sepsis
Authors: Kirsi-Maija Kaukonen, Michael Bailey, David Pilcher, D. Jamie Cooper, Rinaldo Bellomo
Journal: New England Journal of Medicine (2015)

The consensus definition of severe sepsis requires suspected or proven infection, organ failure, and signs that meet two or more criteria for the systemic inflammatory response syndrome (SIRS). We aimed to test the sensitivity, face validity, and construct validity of this approach.We studied data from patients from 172 intensive care units in Australia and New Zealand from 2000 through 2013. We identified patients with infection and organ failure and categorized them according to whether they had signs meeting two or more SIRS criteria (SIRS-positive severe sepsis) or less than two SIRS criteria (SIRS-negative severe sepsis). We compared their characteristics and outcomes and assessed them for the presence of a step increase in the risk of death at a threshold of two SIRS criteria.Of 1,171,797 patients, a total of 109,663 had infection and organ failure. Among these, 96,385 patients (87.9%) had SIRS-positive severe sepsis and 13,278 (12.1%) had SIRS-negative severe sepsis. Over a period of 14 years, these groups had similar characteristics and changes in mortality (SIRS-positive group: from 36.1% [829 of 2296 patients] to 18.3% [2037 of 11,119], P<0.001; SIRS-negative group: from 27.7% [100 of 361] to 9.3% [122 of 1315], P<0.001). Moreover, this pattern remained similar after adjustment for baseline characteristics (odds ratio in the SIRS-positive group, 0.96; 95% confidence interval [CI], 0.96 to 0.97; odds ratio in the SIRS-negative group, 0.96; 95% CI, 0.94 to 0.98; P=0.12 for between-group difference). In the adjusted analysis, mortality increased linearly with each additional SIRS criterion (odds ratio for each additional criterion, 1.13; 95% CI, 1.11 to 1.15; P<0.001) without any transitional increase in risk at a threshold of two SIRS criteria.The need for two or more SIRS criteria to define severe sepsis excluded one in eight otherwise similar patients with infection, organ failure, and substantial mortality and failed to define a transition point in the risk of death. (Funded by the Australian and New Zealand Intensive Care Research Centre.).
Viral CNS infections in children from a malaria-endemic area of Malawi: a prospective cohort study
Authors: Macpherson Mallewa, Pam Vallely, Brian Faragher, Dan Banda, Paul Klapper, Mavuto Mukaka, Harriet Khofi, Paul Pensulo, Terrie Taylor, Malcolm Molyneux, Tom Solomon
Journal: The Lancet Global Health (2013)

BackgroundFever with reduced consciousness is an important cause of hospital admission of children in sub-Saharan Africa, with high mortality. Cerebral malaria, diagnosed when acute Plasmodium falciparum infection and coma are recorded with no other apparent reason, is one important cause. We investigated whether viruses could also be an important cause of CNS infection in such patients, and examined the relative contribution of viral pathogens and malaria parasitaemia.MethodsWe did a prospective cohort study in Blantyre, Malawi. From March 1, 2002, to Aug 31, 2004, we enrolled children aged between 2 months and 15 years who were admitted to hospital with suspected non-bacterial CNS infections. Children with a cerebrospinal fluid (CSF) white cell count of less than 1000 cells per μL and negative bacterial microscopy and culture were deemed to have suspected viral CNS infection. Blood was examined for asexual forms of P falciparum. PCR was done on CSF or on post-mortem brain biopsy specimens to detect 15 viruses known to cause CNS infection.FindingsFull outcome data were available for 513 children with suspected viral CNS infection, of whom 94 (18%) died. 163 children (32%) had P falciparum parasitaemia, of whom 34 (21%) died. At least one virus was detected in the CNS in 133 children (26%), of whom 43 (33%) died. 12 different viruses were detected; adenovirus was the most common, affecting 42 children; mumps, human herpes virus 6, rabies, cytomegalovirus, herpes simplex virus 1, and enterovirus were also important. 45 (9%) of the 513 children had both parasitaemia and viral infection, including 27 (35%) of 78 diagnosed clinically with cerebral malaria. Children with dual infection were more likely to have seizures than were those with parasitaemia alone, viral infection only, or neither (p<0·0001). 17 (38%) of the 45 children with dual infection died, compared with 26 (30%) of 88 with viral infection only, 17 (14%) of 118 with parasitaemia only, and 34 (13%) of 262 with neither (p<0·0001). Logistic regression showed children with a viral CNS infection had a significantly higher mortality than did those who did not have a viral CNS infection (p=0·001).InterpretationViral CNS infections are an important cause of hospital admission and death in children in Malawi, including in children whose coma might be attributed solely to cerebral malaria. Interaction between viral infection and parasitaemia could increase disease severity.FundingWellcome Trust, US National Institutes of Health, and UK Medical Research Council.