tbuckley/cabot-search huggingface dataset:
Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia
Authors: V. Yap
Journal: JAMA (1976)

In two patients, severe hyperkalemia and serious cardiac arrhythmia developed after excessive use of potassium-containing salt substitutes. Both had impaired ability to handle and excrete additional potassium load due to chronic congestive heart failure, azotemia, and administration of spironolactone. Prompt recognition of the arrhythmia and immediate restoration of the cardiac rate and rhythm by pacemaker support followed by intensive regimen to lower the serum potassium prevented a potentially fatal outcome. These cases emphasize the potential danger of salt substitutes when used by patients who are predisposed to retain potassium. (<i>JAMA</i>236:2775-2776, 1976)
Increased Sympathetic Nerve Activity in Pulmonary Artery Hypertension
Authors: Sonia Velez-Roa, Agnieszka Ciarka, Boutaina Najem, Jean-Luc Vachiery, Robert Naeije, Philippe van de Borne
Journal: Circulation (2004)

This study tested the hypothesis that sympathetic nerve activity is increased in pulmonary artery hypertension (PAH), a rare disease of poor prognosis and incompletely understood pathophysiology. We subsequently explored whether chemoreflex activation contributes to sympathoexcitation in PAH.We measured muscle sympathetic nerve activity (MSNA) by microneurography, heart rate (HR), and arterial oxygen saturation (Sao(2)) in 17 patients with PAH and 12 control subjects. The patients also underwent cardiac echography, right heart catheterization, and a 6-minute walk test with dyspnea scoring. Circulating catecholamines were determined in 8 of the patients. Chemoreflex deactivation by 100% O(2) was assessed in 14 patients with the use of a randomized, double-blind, placebo-controlled, crossover study design. Compared with the controls, the PAH patients had increased MSNA (67+/-4 versus 40+/-3 bursts per minute; P<0.0001) and HR (82+/-4 versus 68+/-3 bpm; P=0.02). MSNA in the PAH patients was correlated with HR (r=0.64, P=0.006), Sao(2) (r=-0.53, P=0.03), the presence of pericardial effusion (r=0.51, P=0.046), and NYHA class (r=0.52, P=0.033). The PAH patients treated with prostacyclin derivatives had higher MSNA (P=0.009), lower Sao(2) (P=0.01), faster HR (P=0.003), and worse NYHA class (P=0.04). Plasma catecholamines were normal. Peripheral chemoreflex deactivation with hyperoxia increased Sao(2) (91.7+/-1% to 98.4+/-0.2%; P<0.0001) and decreased MSNA (67+/-5 to 60+/-4 bursts per minute; P=0.0015), thereby correcting approximately one fourth of the difference between PAH patients and controls.We report for the first time direct evidence of increased sympathetic nerve traffic in advanced PAH. Sympathetic hyperactivity in PAH is partially chemoreflex mediated and may be related to disease severity.
Montelukast and Churg-Strauss syndrome
Authors: B J LIPWORTH
Journal: Thorax (2001)

I read with interest the case report by Tuggey and Hosker where Churg-Strauss syndrome was associated with the use of montelukast in an asthmatic patient in whom there was no recent exposure to oral corticosteroid.1 However, it is worth noting that the patient was using a high dose of inhaled fluticasone propionate (1.5 mg/day) via a large volume spacer prior to the introduction of montelukast. In this respect, a large volume spacer has been shown to double the systemic bioavailability of fluticasone propionate compared with a metered dose inhaler, in terms of its propensity for adrenal suppression.2 In a dose ranging study in asthmatic patients a comparison was made between inhaled fluticasone propionate via a 750 ml large volume spacer (Volumatic) and oral prednisolone.3 Regression analysis showed significant (p<0.05) dose-response relationships with both drugs for suppression of peripheral blood eosinophils (fig 1), in keeping with their systemic bioavailability. At the highest doses studied for prednisolone (20 mg/day) and fluticasone propionate (2 mg/day nominal dose) there was a 1.5-fold (95% CI 0.8 to 2.7) greater suppression of blood eosinophils with prednisolone than with fluticasone although, as indicated by the confidence interval (which included unity), this did not represent a significant …
Blood groups and plasma cholesterol esterification
Authors: E. J. WAKLEY, M. J. S. LANGMAN
Journal: Cardiovascular Research (1973)

Journal Article Blood groups and plasma cholesterol esterification Get access E. J. WAKLEY, E. J. WAKLEY 2 From the University Department of Medicine, General Hospital, Nottingham 2Present address: Freedom Fields Hospital, Plymouth. Search for other works by this author on: Oxford Academic PubMed Google Scholar M. J. S. LANGMAN M. J. S. LANGMAN From the University Department of Medicine, General Hospital, Nottingham Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 7, Issue 5, September 1973, Pages 676–678, https://doi.org/10.1093/cvr/7.5.676 Published: 01 September 1973
Fibroblast Growth Factor 21 Predicts the Metabolic Syndrome and Type 2 Diabetes in Caucasians
Authors: Thomas Bobbert, Franziska Schwarz, Antje Fischer-Rosinsky, Andreas F.H. Pfeiffer, Matthias Möhlig, Knut Mai, Joachim Spranger
Journal: Diabetes Care (2012)

OBJECTIVE The incidence of the metabolic syndrome and type 2 diabetes mellitus (T2DM) is rising worldwide. Liver-derived fibroblast growth factor (FGF)-21 affects glucose and lipid metabolism. The aim of this study was to analyze the predictive value of FGF-21 on the incidence of T2DM and the metabolic syndrome. RESEARCH DESIGN AND METHODS The Metabolic Syndrome Berlin Potsdam (MeSyBePo) recall study includes 440 individuals. Glucose metabolism was analyzed using an oral glucose tolerance test, including insulin measurements. FGF-21 was measured using enzyme-linked immunosorbent assay. Primary study outcome was diabetes and the metabolic syndrome incidence and change of glucose subtraits. RESULTS During a mean follow-up of 5.30 ± 0.1 years, 54 individuals developed the metabolic syndrome, 35 developed T2DM, and 69 with normal glucose tolerance at baseline progressed to impaired glucose metabolism, defined as impaired fasting glucose, impaired glucose tolerance, or T2DM. FGF-21 predicted incident metabolic syndrome (lnFGF-21 odds ratio [OR] 2.6 [95% CI 1.5 – 4.5]; P = 0.001), T2DM (2.4 [1.2–4.7]; P = 0.01), and progression to impaired glucose metabolism (2.2 [1.3 – 3.6]; P = 0.002) after adjustment for age, sex, BMI, and follow-up time. Additional adjustment for waist-to-hip ratio, systolic blood pressure, HDL cholesterol, triglycerides, and fasting glucose did not substantially modify the predictive value of FGF-21. CONCLUSIONS FGF-21 is an independent predictor of the metabolic syndrome and T2DM in apparently healthy Caucasians. These results may indicate FGF-21 resistance precedes the onset of the metabolic syndrome and T2DM.
Incidence, Causes, and Survival Trends From Cardiovascular-Related Sudden Cardiac Arrest in Children and Young Adults 0 to 35 Years of Age
Authors: Lauren Meyer, Benjamin Stubbs, Carol Fahrenbruch, Chris Maeda, Kimberly Harmon, Mickey Eisenberg, Jonathan Drezner
Journal: Circulation (2012)

Background— Sudden cardiac arrest is a leading cause of death in children and young adults. This study determined the incidence, cause, and outcomes of cardiovascular-related out-of-hospital cardiac arrest (OHCA) in individuals &lt;35 years of age. Methods and Results— A retrospective cohort of OHCA in children and young adults from 1980 through 2009 was identified from the King County (Washington) Division of Emergency Medical Services' Cardiac Arrest Database. Incidence was calculated from population census data and causes of arrest determined by review of autopsy reports and all available medical records. A total of 361 cases (26 cases 0–2 years of age, 30 cases 3–13 years of age, 60 cases 14–24 years of age, and 245 cases 25–35 years of age) of OHCA were treated by emergency medical services responders, for an overall incidence of 2.28 per 100 000 person-years (2.1 in those 0–2 years of age, 0.61 in those 3–13 years of age, 1.44 in those 14–24 years of age, and 4.40 in those 25–35 years of age). The most common causes of OHCA were congenital abnormalities in those 0 to 2 years of age (84.0%) and 3 to 13 years of age (21%), presumed primary arrhythmia in those 14 to 24 of age (23.5%), and coronary artery disease in those 25 to 35 years of age (42.9%). The overall survival rate was 26.9% (3.8% in those 0–2 years of age, 40.0% in those 3–13 years of age, 36.7% in those 14–24 years of age, and 27.8% in those 25–35 years of age). Survival increased throughout the study period from 13.0% in 1980 to 1989 to 40.2% in 2000 to 2009 ( P &lt;0.001). Conclusions— The incidence of OHCA in children and young adults is higher than previously reported, and a more specific understanding of the causes should guide future prevention programs. Survival trends support contemporary resuscitation protocols for OHCA in the young.
Postoperative pulmonary complications following thoracic surgery: are there any modifiable risk factors?
Authors: P. Agostini, H. Cieslik, S. Rathinam, E. Bishay, M. S. Kalkat, P. B. Rajesh, R. S. Steyn, S. Singh, B. Naidu
Journal: Thorax (2010)

<h3>Background</h3> Postoperative pulmonary complications (PPC) are the most frequently observed complications following lung resection, of which pneumonia and atelectasis are the most common. PPCs have a significant clinical and economic impact associated with increased observed number of deaths, morbidity, length of stay and associated cost. The aim of this study was to assess the incidence and impact of PPCs and to identify potentially modifiable independent risk factors. <h3>Methods</h3> A prospective observational study was carried out on all patients following lung resection via thoracotomy in a regional thoracic centre over 13 months. PPC was assessed using a scoring system based on chest x-ray, raised white cell count, fever, microbiology, purulent sputum and oxygen saturations. <h3>Results</h3> Thirty-four of 234 subjects (14.5%) had clinical evidence of PPC. The PPC patient group had a significantly longer length of stay (LOS) in hospital, high dependency unit (HDU) LOS, higher frequency of intensive care unit (ITU) admission and a higher number of hospital deaths. Older patients, body mass index (BMI) ≥30 kg/m<sup>2</sup>, preoperative activity &lt;400 m, American Society of Anesthesiologists (ASA) score ≥3, smoking history, chronic obstructive pulmonary disease (COPD), lower preoperative forced expiratory volume in 1 s (FEV<sub>1</sub>) and predicted postoperative (PPO) FEV<sub>1</sub> were all significantly (p&lt;0.05) associated with PPC on univariate analysis. Multivariate analysis confirmed that age &gt;75 years, BMI ≥30 kg/m<sup>2</sup>, ASA ≥3, smoking history and COPD were significant independent risk factors in the development of PPC (p&lt;0.05). <h3>Conclusion</h3> The clinical impact of PPCs is marked. Significant independent preoperative risk factors have been identified in current clinical practice. Potentially modifiable risk factors include BMI, smoking status and COPD. The impact of targeted therapy requires further evaluation.
Influence of Admixture and Paleolithic Range Contractions on Current European Diversity Gradients
Authors: Miguel Arenas, Olivier François, Mathias Currat, Nicolas Ray, Laurent Excoffier
Journal: Molecular Biology and Evolution (2012)

Cavalli-Sforza and Edwards (Analysis of human evolution. 1963. In: Geerts SJ, editor. Genetics today: Proceedings of the 11th International Congress of Genetics, The Hague, The Netherlands. New York: Pergamon. p. 923-993.) initiated the representation of genetic relationships among human populations with principal component (PC) analysis (PCA). Their study revealed the presence of a southeast-northwest (SE-NW) gradient of genetic variation in current European populations, which was interpreted as the result of the demic diffusion of early neolithic farmers during their expansion from the near east. However, this interpretation has been questioned, as PCA gradients can occur even when there is no expansion and because the first PC axis is often orthogonal to the expansion axis. Here, we revisit PCA patterns obtained under realistic scenarios of the settlement of Europe, focusing on the effects of various levels of admixture between paleolithic and neolithic populations, and of range contractions during the last glacial maximum (LGM). Using extensive simulations, we find that the first PC (PC1) gradients are orthogonal to the expansion axis, but only when the expansion is recent (neolithic). More ancient (paleolithic) expansions alter the orientation of the PC1 gradient due to a spatial homogenization of genetic diversity over time, and to the exact location of LGM refugia from which re-expansions proceeded. Overall we find that PC1 gradients consistently follow an SE-NW orientation if there is a large paleolithic contribution to the current European gene pool, and if the main refuge area during the last ice age was in the Iberian Peninsula. Our study suggests that an SE-NW PC1 gradient is compatible with little genetic impact of neolithic populations on the current European gene pool, and that range contractions have affected observed genetic patterns.
Influence of Gemfibrozil and Clofibrate on Metabolism of Cholesterol and Plasma Triglycerides in Man
Authors: Y. A. Kesaniemi, Scott M Grundy
Journal: JAMA (1984)

Mechanisms for the hypolipidemic action of gemfibrozil were examined in seven patients with hypertriglyceridemia. In addition, seven hyperlipidemic patients were studied with and without clofibrate treatment to compare the mechanisms by which these two drugs lower plasma triglyceride levels. All patients were studied on a metabolic ward. The first month was a control period, followed by one month of either gemfibrozil or clofibrate therapy. During treatment with gemfibrozil, plasma total triglyceride levels decreased by an average of 51%, and triglyceride levels in very low—density lipoproteins (VLDLs) fell by 57%. Transport rates of VLDL triglyceride were determined by multicompartmental analysis following injection of tritiated glycerol as a precursor. Gemfibrozil decreased transport (production) of VLDL triglyceride by an average of 28% and increased the fractional catabolic rate (FCR) of VLDL triglyceride by 92%. Clofibrate reduced plasma total triglyceride values on an average of 32% and VLDL triglyceride values by 38%. In contrast to gemfibrozil, clofibrate did not change transport rates of VLDL triglyceride but increased the fractional catabolic rate of VLDL triglyceride by 35%. Gemfibrozil thus decreased production of VLDL triglyceride<i>and</i>enhanced its clearance, while clofibrate only increased clearance of VLDL triglyceride. On the average, plasma cholesterol levels did not fall during gemfibrozil treatment, but levels of cholesterol in high-density lipoproteins and in low-density lipoproteins increased by 31% and 11%, respectively. The drug produced a 30% increase in fecal excretion of neutral steroids and a 37% decrease in fecal excretion of bile acids. Outputs of total neutral steroids and net cholesterol balance thus remained unchanged. (<i>JAMA</i>1984;251:2241-2246)
Features of Chronic Hemodialysis Practice after the Marmara Earthquake
Authors: Mehmet Sukru Sever, Ekrem Erek, Raymond Vanholder, Aykut Kalkan, Nevin Guney, Nesrin Usta, Cevdet Yilmaz, Cavit Kutanis, Ramazan Turgut, Norbert Lameire
Journal: Journal of the American Society of Nephrology (2004)

After disasters, treatment of chronic hemodialysis (HD) patients is problematic because of logistic and medical reasons. This study analyzes features of HD practice in the regions affected by the Marmara earthquake that struck northwestern Turkey in August 1999. Questionnaires asking about HD infrastructure, medical/social problems of chronic dialysis patients, and the fate of dialysis personnel after the disaster were sent to dialysis units located in the affected region. Data gathered from eight HD centers that responded to questionnaires were then analyzed. The number of HD centers and machines were 12 and 124, respectively, before the earthquake. The number of weekly HD sessions in the analyzed eight centers declined from 1093 before the disaster to 520, 616, and 729 1 wk, 1 mo, and 3 mo after the earthquake, respectively. In the effective seven centers, the number of HD personnel was 112 before the earthquake, which dropped to 86 and 94 1 and 3 mo after the disaster, respectively. Overall, there were 439 patients in the analyzed eight centers before the disaster, whereas data were provided on 356 (212 were male; mean age, 47.6 +/- 15.1 yr) dialysis patients. Six patients died, and seven were seriously and 28 mildly injured by the direct effects of trauma. The percentage of patients who received once-weekly dialysis increased from 2.3 to 7.2% within the first week, with a return to lower figures (4.1 and 2.8%) 1 and 3 mo afterward. Despite a decrease in the number of HD sessions, interdialytic weight gain decreased 1 wk after the disaster and BP measurements did not change significantly before and after the earthquake. A total of 301 and 31 patients left their dialysis centers, temporarily and permanently. After catastrophic earthquakes, despite a decrease in the number of HD sessions, patients comply with disaster conditions, likely by strictly following dietary and fluid restrictions.
Mucus-Penetrating Nanoparticles for Vaginal Drug Delivery Protect Against Herpes Simplex Virus
Authors: Laura M. Ensign, Benjamin C. Tang, Ying-Ying Wang, Terence A. Tse, Timothy Hoen, Richard Cone, Justin Hanes
Journal: Science Translational Medicine (2012)

Incomplete coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides, for preventing sexually transmitted infections. We investigated vaginal distribution, retention, and safety of nanoparticles with surfaces modified to enhance transport through mucus. We show that mucus-penetrating particles (MPPs) provide uniform distribution over the vaginal epithelium, whereas conventional nanoparticles (CPs) that are mucoadhesive are aggregated by mouse vaginal mucus, leading to poor distribution. Moreover, when delivered hypotonically, MPPs were transported advectively (versus diffusively) through mucus deep into vaginal folds (rugae) within minutes. By penetrating into the deepest mucus layers, more MPPs were retained in the vaginal tract after 6 hours compared to CPs. After 24 hours, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPPs. We then developed MPPs composed of acyclovir monophosphate (ACVp). When administered before vaginal herpes simplex virus 2 challenge, ACVp-MPPs protected 53% of mice compared to only 16% protected by soluble drug. Overall, MPPs improved vaginal drug distribution and retention, provided more effective protection against vaginal viral challenge than soluble drug, and were nontoxic when administered daily for 1 week.
Lack of neuroprotection in the absence of P2X7 receptors in toxin-induced animal models of Parkinson's disease
Authors: Zsuzsanna Hracskó, Mária Baranyi, Cecilia Csölle, Flóra Gölöncsér, Emilia Madarász, Ágnes Kittel, Beáta Sperlágh
Journal: Molecular Neurodegeneration (2011)

Abstract Background Previous studies indicate a role of P2X 7 receptors in processes that lead to neuronal death. The main objective of our study was to examine whether genetic deletion or pharmacological blockade of P2X 7 receptors influenced dopaminergic cell death in various models of Parkinson's disease (PD). Results mRNA encoding P2X 7 and P2X 4 receptors was up-regulated after treatment of PC12 cells with 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). P2X 7 antagonists protected against MPTP and rotenone induced toxicity in the LDH assay, but failed to protect after rotenone treatment in the MTT assay in PC12 cells and in primary midbrain culture. In vivo MPTP and in vitro rotenone pretreatments increased the mRNA expression of P2X 7 receptors in the striatum and substantia nigra of wild-type mice. Basal mRNA expression of P2X 4 receptors was higher in P2X 7 knockout mice and was further up-regulated by MPTP treatment. Genetic deletion or pharmacological inhibition of P2X 7 receptors did not change survival rate or depletion of striatal endogenous dopamine (DA) content after in vivo MPTP or in vitro rotenone treatment. However, depletion of norepinephrine was significant after MPTP treatment only in P2X 7 knockout mice. The basal ATP content was higher in the substantia nigra of wild-type mice, but the ADP level was lower. Rotenone treatment elicited a similar reduction in ATP content in the substantia nigra of both genotypes, whereas reduction of ATP was more pronounced after rotenone treatment in striatal slices of P2X 7 deficient mice. Although the endogenous amino acid content remained unchanged, the level of the endocannabinoid, 2-AG, was elevated by rotenone in the striatum of wild-type mice, an effect that was absent in mice deficient in P2X 7 receptors. Conclusions We conclude that P2X 7 receptor deficiency or inhibition does not support the survival of dopaminergic neurons in an in vivo or in vitro models of PD.
Differential Constitutive Activation of the Epidermal Growth Factor Receptor in Non–Small Cell Lung Cancer Cells Bearing<i>EGFR</i>Gene Mutation and Amplification
Authors: Takafumi Okabe, Isamu Okamoto, Kenji Tamura, Masaaki Terashima, Takeshi Yoshida, Taroh Satoh, Minoru Takada, Masahiro Fukuoka, Kazuhiko Nakagawa
Journal: Cancer Research (2007)

The identification of somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC) and the association of such mutations with the clinical response to EGFR tyrosine kinase inhibitors (TKI), such as gefitinib and erlotinib, have had a substantial effect on the treatment of this disease. EGFR gene amplification has also been associated with an increased therapeutic response to EGFR-TKIs. The effects of these two types of EGFR alteration on EGFR function have remained unclear, however. We have now examined 16 NSCLC cell lines, including eight newly established lines from Japanese NSCLC patients, for the presence of EGFR mutations and amplification. Four of the six cell lines that harbor EGFR mutations were found to be positive for EGFR amplification, whereas none of the 10 cell lines negative for EGFR mutation manifested EGFR amplification, suggesting that these two types of EGFR alteration are closely associated. Endogenous EGFRs expressed in NSCLC cell lines positive for both EGFR mutation and amplification were found to be constitutively activated as a result of ligand-independent dimerization. Furthermore, the patterns of both EGFR amplification and EGFR autophosphorylation were shown to differ between cell lines harboring the two most common types of EGFR mutation (exon 19 deletion and L858R point mutation in exon 21). These results reveal distinct biochemical properties of endogenous mutant forms of EGFR expressed in NSCLC cell lines and may have implications for treatment of this condition.