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Background Prognosis in HFpEF is determined by risk factor control and treatment of comorbidities. Industrially processed TFA (IP-TFA) from partially hydrogenated oils have been linked to altered lipoprotein metabolism, endothelial dysfunction, increased biomarkers of inflammation and increased NTproBNP. In patients with heart failure with preserved ejection fraction (HFpEF), associations of TFA blood levels with patient characteristics are unknown. Purpose To evaluate associations of blood TFA with cardiovascular risk factors, aerobic capacity and cardiac function in patients with HFpEF. Methods This is a secondary analysis from the Aldo-DHF-RCT. From 422 patients, individual blood TFA were analyzed at baseline in n=404 using the HS-Omega-3-Index® methodology. Patient characteristics were; 67±8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥50%, E/e' 7.1±1.5; median NT-proBNP 158 ng/L (IQR 82–298). Multiple linear regression analyses, using sex and age as covariates, were used to describe associations of TFA with metabolic phenotype, functional capacity, echocardiographic markers for left ventricular diastolic function (LVDF), and neurohumoral activation at baseline and after 12-months-follow-up (12mFU). To account for randomization group, all analyses were repeated as sensitivity analysis with group as covariate. A significance level of α=5% was used for all tests. As all tests were hypothesis generating without confirmatory interpretation, no correction was applied to counteract the problem of multiple comparisons. Results Higher blood levels of the naturally occurring TFA C16:1n-7t were broadly associated with a more favorable lipid profile, lower body weight/central adiposity, lower white blood cell count and lower biochemical markers of non-alcoholic fatty liver disease at baseline/12mFU. Conversely, blood levels of the IP-TFA C18:1n9t were directly associated with lipid risk markers [triglycerides (β=19.7, p Conclusions In HFpEF patients, higher blood levels of industrially processed TFA, but not of the TFA C16:1n-7t in full fat dairy and meat, were associated with a higher risk phenotype and lower aerobic capacity. Our findings support efforts to remove IP-TFA from the food supply for improving risk factor control in HFpEF patients. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Foundation of Heart Research

Endocrine disorders are the most common causes of secondary hypertension. Early diagnosis and specific treatment are crucial for improvement of the prognosis. This article provides an overview on which clinical constellations point to an increased risk of secondary causes of hypertension. These include spontaneous hypokalemia, young age at onset of hypertension, adrenal incidentaloma and therapy refractive arterial hypertension. The basic diagnostics include determination of the aldosterone to renin ratio, measurement of free plasma metanephrines and a 1 mg dexamethasone suppression test. Borderline results require repeated control testing and/or confirmatory testing under standardized test conditions. In cases of repeatedly conspicuous results referral to a specialized clinic should be considered for further clarification and confirmation of the diagnosis. Imaging diagnostics may constitute an adjunct to laboratory testing after the diagnosis has been confirmed. Therapeutic algorithms vary depending on the underlying endocrine disease.

Track quality is a determinant factor for evaluating the overall performance of vehicle track interaction with respect to safety, ride quality and maintenance. Important parameters specifying the general quality of the track include track geometry (undamped) and track stiffness (damped), which can be evaluated by measurements taken along with track sections. A new co-simulation model based on Finite Element Method (FEM) and Multi Body Simulation (MBS) is built for the detailed description of track quality and its contribution to vehicle track interaction without simplifying the track structure as interconnected single elements. The simulation models and tools have been validated with the help of measured track geometry, track stiffness and dynamic wheel rail forces along the track sections of high speed lines. A comparative study between high speed lines using conventional ballasted track and ballastless track showed a significantly better quality in ballastless track sections. The dynamic forces which were determined by simulations and verified by measurements along the ballastless track section were comparatively less than the specified limits by German regulations for ballastless track design. Lower levels of dynamic forces can be utilized for optimization of track design and installation procedures with respect to lower initial costs.

Fragestellung: Induzuieren inflammatorische Zytokine am Geburtstermin die intrauterine Prostaglandinsekretion? Methoden: Die Konzentration an Il-6, Il-lβ, TNF-α, PGE2 und PGF2α wurden im Zervixsekret und Fruchtwasser wahrend des Geburtsverlaufs bestimmt, sowie deren Sekretion von kultivierten Amnion-, Chorion-, Dezidua- und Trophoblastzellen nach elektiver Sektio (wehenloser Uterus) und Spontanpartus (maximale Wehentatigkeit) gemessen. Ergebnisse: Zeitgerechte Wehentatigkeit am Termin ist mit massiver intrauteriner Zytokin- und Prostaglandinsekretion assoziiert. Dabei werden sowohl Zytokine als auch Prostaglandine ausschlieβlich von fetalen Trophoblastzellen verstarkt produziert. Schluβfolgerungen: Das Signal zur Geburtseinleitung am Termin ist fetalen Ursprungs.

An apparatus has been developed to measure the longitudinal spherical aberration of soft contact lenses in a configuration that closely simulates the in vivo situation. This was achieved by a special mounting method: the soft lens is held by a transparent elastic membrane against the first surface of a zero-power substrate lens system having the same anterior radius as the mean human cornea. Measurements of the longitudinal spherical aberration of some typical soft contact lenses are given.

Summary Preeclampsia is a disease of unknown etiology and a major contributor to maternal and neonatal morbidity and mortality. In severe preeclampsia, intravascular volume depletion and susceptibility of developing pulmonary edema complicate the anesthetic management. Invasive monitors are often required for optimal patient management, with central venous or pulmonary artery pressure measurements being particularly useful for guiding volume resuscitation. In our practice, lumbar epidural blockade is the preferred method for providing analgesia and anesthesia; however, the block must be induced slowly in order to minimize sudden hemodynamic changes and to permit optimal fluid management.

Advanced glycosylation end-products (AGE) in human blood and urine were investigated with the aid of an AGE-specific enzyme-linked immunosorbent assay. Evidence is presented that AGE are natural constituents of human serum and urine. In diabetics with normal renal function only a small increase in serum AGE levels was found as compared to normal controls, while no difference in urinary excretion rate was discernible. Urinary excretion rate of AGE from diabetic and non-diabetic patients with end-stage renal disease was reduced, while high serum AGE levels were observed. AGE in serum occur in a low-molecular-weight fraction and in a possibly protein-bound high-molecular-weight fraction. In urine from normal controls three immunologically reactive fractions were detected whose apparent molecular mass ranged from 100 to 1000 Daltons, while in urine from patients with end-stage renal failure additional high-molecular-weight fractions appeared.

Advanced glycosylation end-products (AGE) in human blood and urine were investigated with the aid of an AGE-specific enzyme-linked immunosorbent assay. Evidence is presented that AGE are natural constituents of human serum and urine. In diabetics with normal renal function only a small increase in serum AGE levels was found as compared to normal controls, while no difference in urinary excretion rate was discernible. Urinary excretion rate of AGE from diabetic and non-diabetic patients with end-stage renal disease was reduced, while high serum AGE levels were observed. AGE in serum occur in a low-molecular-weight fraction and in a possibly protein-bound high-molecular-weight fraction. In urine from normal controls three immunologically reactive fractions were detected whose apparent molecular mass ranged from 100 to 1000 Daltons, while in urine from patients with end-stage renal failure additional high-molecular-weight fractions appeared.

Induce infection-associated cytokines intrauterine secretion of prostaglandins and term labor?Concentrations of Il-6, Il-1 beta, TNF-alpha, PGF2 and PGF2 alpha were determined in cervical secretions and amniotic fluid during spontaneous term labor. The supernatant of amnion-, chorion-, decidua- and trophoblast cells, cultured after elective cesarean section or spontaneous delivery, was analysed for cytokine- and prostaglandin activity.Term labor always is associated with intrauterine cytokine- and prostaglandin release. Increased production of cytokines and prostaglandins in case of normal term labor only was found by fetal trophoblast cells.Signal for parturition is of trophoblast and therefore of fetal origin.

Tachycardia often limits the usefulness of conventional beta-adrenergic inotropic therapy; therefore, a compound possessing positive inotropic but not chronotropic properties would be useful. These experiments determined the inotropic and chronotropic properties of naloxone in spontaneously contracting guinea pig atria and electrically paced papillary muscles in the presence and absence of isoproterenol. In atria naloxone exhibited no significant intrinsic inotropic properties. In the presence of isoproterenol, naloxone increased contractility in spontaneously contracting atria and electrically paced ventricular tissues by 11% and 79% respectively, without any significant change in contraction rate. Since naloxone potentiated the inotropic but not chronotropic effects of isoproterenol, it may be a useful adjunct to conventional beta-adrenergic therapy where an inotropic but not chronotropic effect is desired.

Naloxone potentiates the effects of adrenergic agonists when administered to hypovolemic dogs, and it has been assumed that this effect is due to naloxone's action at opiate receptors. To help determine the site and mechanism of this interaction, we administered naloxone and its "d" stereo-isomer (which does not bind to opiate receptors) to guinea pig papillary muscles in the presence and absence of pharmacologic (isoproterenol) and physiologic (treppe) inotropic stimulation. In control muscles and in rapidly paced muscles, naloxone was without significant inotropic effect. In the presence of isoproterenol, d- and l-naloxone exerted significant positive inotropic effects that were dose dependent. We conclude that, since both d- and l-naloxone potentiated the inotropic effects of isoproterenol and this was seen in the absence of opioids, naloxone may increase contractility by a nonopiate receptor-mediated mechanism.

~~ Abstract. This study explored the hypothesis that coronary vascular injury and dysfunction result from intracoronary administration of Escherichia coli endotoxin (0.025 to 0.4 mg/kg) in dogs. Peak hyperemic coronary flow following a 15-sec period of stopped flow and the maximum flow in response to adenosine were used to estimate coronary vascular reserve. The wet-todry ratio of myocardial tissue was used to estimate extravascular water content as an indicator of vascular leak due to endothelial injury. Intracoronary saline was used as a control. Peak reactive hyperemia and maximum flow at constant coronary pressure were not different in the animals receiving intracoronary endotoxin (n = 6) and the animals receiving saline (n = 5) during 4 hr following treatment. In addition, wet-todry ratios were similar in these two groups. These data fail to support the hypothesis that endotoxin, per se, produces coronary vascular injury of sufficient magnitude to produce myocardial dysfunction. 0 1987 Society for Experimental Biology and Medicine.

Cerebral angiography has come to be one of the most valuable diagnostic procedures in the neurosurgical armamentarium. By injecting a contrast medium into the large vessels supplying circulation to the brain, one can detect and diagnose conditions which were previously impossible to demonstrate. In the development of cerebral angiography, however, many problems have arisen from the irritative effect of the contrast material on the arterial tree and perhaps even on the cerebral substance itself, producing a rather disturbing group of reactions ranging from a mild flushing and tingling sensation to shock and, in some instances, death. In spite of these hazards, as information accumulated it was realized that the procedure was vital, first to the progress of neurosurgery and, more recently, of vascular surgery. The media originally used for angiography were, as in most beginnings, somewhat crude. It was even necessary, some believed, that anesthesia be utilized to allay the patient's suffering during the exa...

The opiate antagonist naloxone increases arterial pressure, maximal left ventricular dp/dt and cardiac output when administered to dogs subjected to hemorrhagic shock. The purpose of this study was to investigate regional blood flow changes associated with naloxone treatment in anesthetized hypovolemic and normovolemic dogs. Hypovolemic dogs (n = 10) were bled over 30 min (t = -30 to t = 0) to a pressure of 45 mm Hg which was maintained for 1 hr. At t = 60, five dogs received naloxone (2 mg/kg + 2 mg/kg X hr), and five received an equal volume of saline. Regional blood flows were determined at t = -30, 45, and 90 min using 15-micron microspheres. Normovolemic dogs (n = 10) were subjected to the same protocol except they were not bled. During hypovolemia, naloxone produced significant increases in myocardial, intestinal, hepatic, and adrenal blood flows whereas saline treatment did not. No significant changes in skin, muscle, fat, pancreatic, renal, or brain flows were detected. The increases in blood flow were not associated with significant changes in vascular resistance. Naloxone had no significant effects on any hemodynamic parameter during normovolemia. The beneficial effects of naloxone in hemorrhagic shock include increased blood flow to vital organs due to increased perfusion pressure which is secondary to improved cardiac performance.

Endogenous opioids are released during stress and appear to contribute to the cardiovascular suppression seen in shock. When the opiate receptor antagonist naloxone is administered intravenously to anesthetized dogs subjected to hemorrhage, mean arterial pressure, maximal left ventricular dp/dt, and cardiac output increase. This study tests the hypothesis that naloxone acts by potentiating the effects of neurally and adrenally released catecholamines. If this hypothesis is correct, then blockade of endogenous catecholamine release should attenuate the response to naloxone, and administration of exogenous adrenergic agonists prior to naloxone treatment should restore the response. Catecholamine release was attenuated by a combination of surgical adrenal denervation and pharmacological ganglionic blockade. Adrenal denervation or chlorisondamine alone attenuated and, in combination, blocked the response to naloxone in hemorrhaged dogs. Infusion of alpha- and beta-adrenergic agonists at a constant rate prior to treatment restored the response to naloxone. Naloxone appears to improve cardiovascular function in hemorrhagic shock by potentiating the effect of released catecholamines and not by increasing sympathoadrenal discharge.

The endogenous opiate ligand, beta-endorphin, is released during stress. We tested the hypothesis that endorphins may be involved in the pathophysiology of hemorrhagic shock by using the opiate receptor blocking agent, naloxone. Two groups of five anesthetized dogs were instrumented to monitor cardiovascular performance and subjected to a protocol in which they were bled into a reservoir to lower mean arterial pressure to 45 mmHg and maintained at that pressure for one hour. At that time the reservoir was clamped and on group of dogs received an intravenous bolus of naloxone (2 mg/kg) and an infusion at 2 mg/kg-hr. These dogs demonstrated a prompt increase in arterial pressure, left ventricular dp/dtmax and cardiac output. The shed blood was returned at t = 2 hr and drug infusion continued for 2 hours. The control group of dogs received saline in equivalent volume. The control dogs died within 30 minutes of clamping the reservoir while all five treated dogs survived beyond 72 hours (P less than 0.02). These data suggest the involvement of endorphins acting on opiate receptors as part of the pathophysiology in this shock model.

The endogenous opioids have been implicated as contributing factors to the cardiovascular dysfunction of shock. Opiate receptor antagonists improve cardiovascular function and long-term survival in laboratory animal models of shock. In this communication, evidence of the therapeutic efficacy of opiate antagonists in canine and primate hemorrhagic shock is presented. The animals were hemorrhaged into a reservoir to lower MAP to 45 mmHg and that pressure was maintained for 1 h at which time the reservoir was clamped and treatment initiated. The “shed blood” was returned at t = 120 min and treatment continued until t = 180 min. Opiate antagonists employed included naloxone, naltrexone and the mixed agonist/antagonist agent, nalbuphine. Both naloxone and naltrexone improved cardiac function at doses of 1 and 2 mg/kg. Animal survival was significantly enhanced in the high dose format. Nalbuphine also improved cardiovascular performance at doses from 1 to 4 mg/kg but at higher doses it depressed cardiac performance. The efficacy of the antagonists is attenuated by acidosis and hypothermia. Opiate antagonists may induce cardiac arrhythmias in combination with beta-adrenergic blocking drugs and the efficacy is reduced in animals that received high dose steroid therapy. Thus the use of opiate antagonists would be contraindicated in patients that received drugs such as propranolol or methylprednisolone. There have been no controlled clinical trials of opiate antagonists in human hemorrhagic shock; these are needed for final clarification.

This article presents the results of functional investigation of the central and peripheral visual fields of 30 patients 3 years after glaucoma surgery. The authors studied the relationship between intraocular pressure and the site of the visual field, and also between vision and the quality of the central visual field. The results of the investigation support the demand for early surgery in glaucoma cases. Patients should be advised and informed thoroughly, because in 36 percent of all cases the cataract grows postoperatively.

Human somatomedins (Sm) show considerable heterogeneity on separation by chromatofocusing (CF). Besides the major forms eluting at pI=8.3 (IGF7I/SmC) and at pI=6.3 (IGF-II) a number of minor peaks emerge which can be classified as IGF-I-like or as IGF-II-like. The aim of the current study was to investigate, whether there is an age-dependence of the polymorphic pattern during human development. Serum (2ml) extracts from children (n=157 and adults (n=9) where fractionated by HPLC-CF. The fractions were screened for Sm-like peptides by CPBA. The total Sm-activity of the various peaks was quantitated either by a specific IGF-I/SmC-RIA or by a IGF-II-RIA giving their relativ contribution to total IGF-I/SmC and IGF-II immunoactivity resp. The results show that the various Sm-like peptides are present in all age groups studied. Although serum IGF-I/SmC rises considerably at the time of puberty, the ratio of the various IGF--I/SmC-like peptides to total IGF-I/SmC-IR did not vary. There was a small but significant increase of the two very basic Sms (pI=9.2 and pI-8.7) from 3.4% at puberty to 6.7% (p