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153 patients (mean age 42 years, range 16-60) who had arterial embolic events were examined prospectively by transthoracic and transoesophageal echocardiography. Patients older than 60 years and those with evidence of extracranial carotid artery occlusive disease were excluded. 84 patients had a cerebral ischaemic event, 50 patients had embolic events in an abdominal organ or limb, and 19 patients had acute retinal ischaemia. The transthoracic echocardiographic examination was normal in 92 patients (60%), whereas only 65 patients (42%) had normal findings after both transthoracic and transoesophageal examination (p<0·005). Intracardiac masses, including valvular vegetations, were found in 39 patients (25%), including 27% of patients with cerebral embolism and 32% of these with peripheral embolism, but in none of the patients with retinal ischaemia (p<0·001). 47 patients (31%) had valvular disease, 10 (7%) had wall motion abnormalities, 23 (15%) had abnormalities of the interatrial septum, and 9 patients (6%) had diseases of the thoracic aorta. Cardiovascular abnormalities were frequently found by echocardiography in patients with arterial emboli. The transoesophageal technique significantly increased the chance of detecting such abnormalities, especially intracardiac masses.

ObjectiveTo investigate the prognostic value of echocardiographic findings in patients who present with symptoms suggestive of acute pulmonary embolism.Design317 patients with clinically suspected pulmonary embolism were prospectively evaluated by echocardiography for the presence of right ventricular afterload stress and right heart or pulmonary artery thrombi. Objective confirmation of pulmonary embolism by lung scan or pulmonary angiography was obtained in 164 (52%). The presence of deep venous thrombosis was established in 90 of 158 patients (57%) who underwent phlebographic or Doppler sonographic studies.ResultsRight ventricular afterload stress was diagnosed in 87 patients (27%). Objective confirmation of pulmonary embolism and diagnosis of deep venous thrombosis was more common in patients with right ventricular afterload stress than in those without (83% v 40% and 46% v 22%, respectively; P &lt; 0·001). This was also true for the detection of thrombi in the right heart and major pulmonary arteries (12 patients v 1 patient; P &lt; 0·001) as well as for the in-hospital mortality from venous thromboembolism (13% v 0·9%; P &lt; 0·001). One year mortality from pulmonary embolism was 13% in patients with right ventricular afterload stress at presentation compared with 1·3% in those without (P &lt; 0·001).ConclusionsThe presence of right ventricular afterload stress detected by echocardiography is a major determinant of short term prognosis in patients with clinically suspected acute pulmonary embolism.

Angiotensin II (AII) is a potent stimulus for HCO3- reabsorption in the rat proximal tubule in vivo. To determine the ionic mechanism of increased HCO3- reabsorption, we have examined the effect of AII on luminal Na(+)-H+ exchange and basolateral Na+/HCO3- cotransport in perfused S1 proximal tubules isolated from superficial nephrons of the rabbit kidney. Transporter activity was assessed by removing Na+ from both luminal and basolateral (i.e., bath) solutions and determining the rate at which intracellular pH (pHi) increased after Na+ was returned to only the lumen or only the bath. pHi was measured with the pH-sensitive fluorescent dye 2', 7'-bis(2-carboxyethyl)-5(and 6)-carboxyfluorescein. We found that basolateral administration of 1 nM AII not only increased the rate of luminal Na(+)-H+ exchange approximately 3.5-fold but also increased the rate of basolateral Na+/HCO3- cotransport approximately 2.5-fold. 5-(N-Ethyl-N-isopropyl)amiloride (50 microM) blocked luminal Na(+)-H+ exchange before and after stimulation by AII but had no effect on basolateral Na+/HCO3- cotransport. Conversely, 4,4'-diisothiocyanato-2,2'-stilbenedisulfonate (50 microM) blocked basolateral Na+/HCO3- cotransport before and after AII but had no effect on luminal Na(+)-H+ exchange. Our data thus indicate that, at least under the conditions of our assay, AII independently stimulates the transporters responsible for both the luminal and basolateral steps of transepithelial HCO3- reabsorption.

Fermentation of nonabsorbed nutrients in the colon generates high concentrations of NH3/NH4+ in the colonic lumen. NH3 is a small, lipophilic neutral weak base that readily permeates almost all cell membranes, whereas its conjugate weak acid NH4+ generally crosses membranes much more slowly. It is not known how colonocytes maintain intracellular pH in the unusual acid-base environment of the colon, where permeant acid-base products of fermentation exist in high concentration. To address this issue, we hand dissected and perfused single, isolated crypts from rabbit proximal colon, adapting techniques from renal-tubule microperfusion. Crypt perfusion permits control of solutions at the apical (luminal) and basolateral (serosal) surfaces of crypt cells. We assessed apical- vs. basolateral-membrane transport of NH3/NH4+ by using fluorescent dyes and digital imaging to monitor intracellular pH of microvacuolated crypt cells as well as luminal pH. We found that, although the basolateral membranes have normal NH3/NH4+ permeability properties, there is no evidence for transport of either NH3 or NH4+ across the apical borders of these crypt cells. Disaggregating luminal mucus did not increase the transport of NH3/NH4+ across the apical border. We conclude that, compared to the basolateral membrane, the apical border of crypt colonocytes has a very low permeability-area product for NH3/NH4+. This barrier may represent an important adaptation for the survival of crypt cells in the environment of the colon.

The kinetic data on model compounds of hemoglobin indicate that in oxyderivatives ligand dissociation rates are sensitive to the "tension" exerted by the proximal base on the metal-to-ligand bond; the corresponding rates for carboxy derivatives are not sensitive to the tension. It is suggested that the metal-to-ligand bond becomes weaker with increased "pull" (or tension) on Fe from the proximal base due to the steric and/or electronic interaction between the ligand, the porphyrin ring, and the proximal base. In model compounds the linear heme Fe-to-CO bound vis-a-vis the bent heme Fe-to-O2 bond probably makes such interactions less significant in carboxy derivatives. It is proposed that the kinetic alpha,beta-chain nonequivalence in Hb4(O2)4 is due to the difference in the tension in the two chains on Fe by the proximal base. The absence of alpha,beta-chain differences large enough to show up in CO dissociation rates from Hb4(CO)4 is explained on the basis of lack of sensitivity of the Fe-CO bound to tension from the proximal base. The implications of the results for the observed cooperative effects in ligand combination (for CO) and dissociation (for O2 and NO) rates of hemoglobin have also been discussed.

The effects of inhibition of the basolateral Na(+)-K(+)-ATPase (pump) on the apical low-conductance K+ channel of principal cells in rat cortical collecting duct (CCD) were studied with patch-clamp techniques. Inhibition of pump activity by removal of K+ from the bath solution or addition of strophanthidin reversibly reduced K+ channel activity in cell-attached patches to 36% of the control value. The effect of pump inhibition on K+ channel activity was dependent on the presence of extracellular Ca2+, since removal of Ca2+ in the bath solution abolished the inhibitory effect of 0 mM K+ bath. The intracellular [Ca2+] (measured with fura-2) was significantly increased, from 125 nM (control) to 335 nM (0 mM K+ bath) or 408 nM (0.2 mM strophanthidin), during inhibition of pump activity. In contrast, cell pH decreased only moderately, from 7.45 to 7.35. Raising intracellular Ca2+ by addition of 2 microM ionomycin mimicked the effect of pump inhibition on K+ channel activity. 0.1 mM amiloride also significantly reduced the inhibitory effect of the K+ removal. Because the apical low-conductance K channel in inside-out patches is not sensitive to Ca2+ (Wang, W., A. Schwab, and G. Giebisch, 1990. American Journal of Physiology. 259:F494-F502), it is suggested that the inhibitory effect of Ca2+ is mediated by a Ca(2+)-dependent signal transduction pathway. This view was supported in experiments in which application of 200 nM staurosporine, a potent inhibitor of Ca(2+)-dependent protein kinase C (PKC), markedly diminished the effect of the pump inhibition on channel activity. We conclude that a Ca(2+)-dependent protein kinase such as PKC plays a key role in the downregulation of apical low-conductance K+ channel activity during inhibition of the basolateral Na(+)-K(+)-ATPase.

We report our resistivity, thermoelectric power and optical investigations on the Ce3Au3Sb4−xnarrow-gap insulator. The resistivity for x=0.12 and 0.17 is characterized by a semiconducting-like behaviour at low temperatures, which contrasts with the metallic-like temperature dependence of the thermoelectric power. This apparent contradiction can be reconciled by a so-called “zero-gap” scenario, as supported by the optical investigation.

This study compares inducibility of ventricular tachyarrhythmias by programmed electrical stimulation of the heart in patients with myocardial infarction with and without reperfusion after streptokinase therapy. Sixtytwo consecutive patients admitted with an acute myocardial infarction were randomized to either combined intravenous and intracoronary streptokinase (streptokinase group) or to standard coronary care unit treatment (control group). Thirty-six of the 62 patients (21 patients from the streptokinase and 15 from the control group) with a first myocardial infarction were studied by programmed ventricular stimulation after a mean of 26 ± 14 days. No patient had a history of antiarrhythmic drug use or documentation of a ventricular arrhythmia before the initial admission.

Summary: We studied the mechanism of K++ channel activation by minoxidil-sulfate (MxSO4) in fused Madin-Darby canine kidney (MDCK) cells. Patch-clamp techniques were used to assess single channel activity, and fluorescent dye techniques to monitor cell calcium. A Ca+2+-dependent inward-rectifying K++ channel with slope conductances of 53±3 (negative potential range) and 20±3 pS (positive potential range) was identified. Channel activity is minimal in cell-attached patches. MxSO4 initiated both transient channel activation and an increase of intracellular Ca+2+ (from 94.2±9.1 to 475±12.6 nmol/liter). The observation that K++ channel activity of excised inside-out patches was detected only at Ca+2+ concentrations in excess of 10 mgrmol/liter suggests the involvement of additional mechanisms during channel activation by MxSO4.Transient K++ channel activity was also induced in cell-attached patches by 10 mgrmol/liter of the protein kinase C activator 1-oleoyl-2-acetyl-glycerol (OAG). OAG (10 mgrmol/liter in the presence of 1.6 mmol/liter ATP) increased the Ca+2 sensitivity of the K+ channel in inside-out patches significantly by lowering the K mfor Ca+2 from 100 mgrmol/liter to 100 nmol/liter. The channel activation by OAG was reversed by the protein kinase inhibitor H8. Staurosporine, a PKC inhibitor, blocked the effect of MxSO4 on K+ channel activation. We conclude that MxSO4-induced K+ channel activity is mediated by the synergistic effects of an increase in intracellular Ca+2 and a PKC-mediated enhancement of the K+ channel's sensitivity to Ca+2.

Summary Isolated early distal tubule cells (EDC) of frog kidney were incubated for 20–28 hr in the presence of aldosterone and then whole-cell K+ currents were measured at constant intracellular pH by the whole-cell voltage-clamp technique. Aldosterone increased barium-inhibitable whole-cell K+ conductance (gK+) threefold. This effect was reduced by amiloride and totally abolished by ouabain. However, aldosterone could still raisegK+ in ouabain-treated cells in the presence of furosemide.

The mechanism of sodium movement across apical membrane of colonic crypt cells of rat distal colon was examined in studies of both 22Na uptake by apical membrane vesicles (AMV) and the rate of intracellular pH (pHi) recovery from an acid load by the addition of lumen sodium. In the presence of chloride but not in its absence, 22Na uptake in crypt AMV was stimulated by an outward gradient of either [H+] or [Na+]. 22Na uptake stimulated by an outward [Na+] gradient was also observed in the presence of other halides in the order of chloride > bromide > fluoride > iodide. pHi recovery from an acid load was both lumen sodium- and chloride-dependent, and the rate of pHi recovery by lumen sodium in the presence of chloride was 65-fold greater than that in the absence of chloride (dpH/dt is 655.4 and 10.2 in the presence and absence of chloride, respectively). One mM amiloride inhibited both [H+] gradient-stimulated 22Na uptake in the presence of chloride in crypt AMV (80%) and lumen sodium- and chloride-dependent pHi recovery in crypt cells (96%). [H+] gradient stimulation of 22Na uptake by crypt AMV in the presence of chloride was less sensitive to amiloride than amiloride inhibition of Na-H exchange in colonic surface AMV. These studies provide compelling evidence that a chloride-dependent Na-H exchange that is relatively amiloride-resistant is present in the apical membrane of colonic crypt cells. As prior studies have not identified a chloride-dependent Na-H exchange, the molecular and functional basis of this novel transport process is not known.

Measurements of thermoelectric power, electrical resistivity, and magnetic susceptibility on new Ce2T3X9-compounds (T=Rh, Ir; X=Al, Ga) are presented. These compounds crystallize in the orthorhombic Y2Co3Ga9-structure. The transport data show for each compound two characteristic anomalies, around 100 K and around 20 K, respectively. In contrast to many Ce-systems, where such anomalies can be ascribed to crystalline-field and Kondo effects, respectively, for these systems the temperature dependence of the susceptibility and the specific heat suggest an intermediate valent Ce-state which shows additional low energy interactions.

The aim of the present study was to obtain detailed information on MDCK cell proton secretion characteristics under various growth conditions. Confluent monolayers cultured on glass coverslips were adapted over 48 h to media with different osmolality and pH (200 mosmol/kgH2O, pH 7.4; 300 mosmol/kgH2O, pH 7.4; and 600 mosmol/kgH2O, pH 6.8) corresponding to the luminal fluid composition of the collecting duct segments found in the in renal cortex, the outer stripe of outer medulla and inner medulla. Proton fluxes were determined from the recovery of intracellular pH following an acid load induced by an NH4Cl pulse times the corresponding intrinsic buffering power (βi). The intracellular buffering power was found to change only with culture medium osmolality but not with culture medium pH. In addition to an amiloride and Hoe-694-sensitive Na+/H+exchange, Madin-Darby canine kidney (MDCK) cells possess a Sch-28080-sensitive, K+-dependent H+extrusion mechanism that is increased upon adaptation of monolayers to hyperosmotic-acidic culture conditions. A significant contribution of the bafilomycin A1-sensitive vacuolar H+-ATPase could be found only in cells adapted to hyposmotic culture conditions. Exposure of MDCK cells to 10−5or 10−7M aldosterone for either 1 or 18 h did not alter the H+extrusion characteristics significantly. The results obtained show that different extracellular osmolality and pH induce different MDCK phenotypes with respect to their H+-secreting systems.

Objectives. This study was undertaken to determine eligibility for and benefit of thrombolytic therapy in patients with acute inferior myocardial infarction with or without right ventricular involvement.

Barucainide is a new class IB antiarrhythmic agent that was studied for efficacy and safety after intravenous administration in patients with severe ventricular arrhythmias. All patients received 80 mg/hr barucainide intravenously for 7 hours or until ventricular arrhythmias were suppressed by greater than 90%. In responders a maintenance dose was given for 24 hours, aimed to achieve steady-state conditions. At baseline and during the treatment and washout periods 24-hour Holter recordings were performed. In addition, electrocardiogram, blood pressure, and plasma concentration of barucainide were measured. In 9 of 12 patients dose titration was effective (mean dose, 185 mg). In six of nine patients arrhythmia suppression persisted during maintenance therapy (mean dose, 18 mg/hr). Plasma concentrations correlated with given doses, rather than with antiarrhythmic efficacy. During the washout period, five patients required more than 12 hours for recurrence of arrhythmias. Treatment was stopped in one patient because of proarrhythmia; one patient had moderate heat sensations. Thus barucainide is a potent class IB agent, with a favorable side effect profile.Clinical Pharmacology and Therapeutics (1991) 49, 78–85; doi:10.1038/clpt.1991.13

In this paper we reviewed some of our work on the photo induced coloration of Poly(p‐phenylene sulfide) (PPS) and compared it to recent results obtained from the thermal treatment of resins that varied in molecular weight and ionic content. The results from this study suggest that coloration of amorphous PPS films after UV irradiation is caused by products different from those that cause coloration in semicrystalline PPS after thermoxidation. In addition, we found that polymer end group chemistry and resin molecular weights play important roles in the thermoxidative coloration of PPS, but only nominally influence the photooxidative coloration of the resin. PPS coloration may arise from the accumulation of specific, colored products (e.g., phenyl‐phenyl moieties) and the possible presence of intermolecular aggregates. The mechanism and extent by which these structures occur in UV irradiated or heated PPS are likely dependent upon the polymer morphology of the samples tested.

We tested the effects of endothelin-1 (ET-1) on intracellular calcium concentration ([Ca2+]i) of cultured M-1 mouse cortical collecting duct cells. [Ca2+]i was measured using fura 2 and a fluorescent imaging system. At a concentration of extracellular calcium ([Ca2+]o) of 1 mM, ET-1 (10(-12) to 10(-7) M) increased [Ca2+]i. A second application of ET-1 had no effect on Ca2+. In contrast, application of arginine vasopressin after an initial exposure to ET-1 induced a second Ca2+ response. In the absence of extracellular Ca2+ (1 mM EGTA) ET-1 also elicited a Ca2+ peak, indicating participation of Ca2+ release from intracellular stores in the initial Ca2+ peak. At [Ca2+]o of 10 mM, ET-1 also induced an intracellular Ca2+ peak but [Ca2+]i remained significantly elevated. The Ca2+ plateau phase was abolished by nickel (10 or 100 microM) and nifedipine (0.1 or 1 microM). We conclude that ET-1 mediates an increase in [Ca2+]i by Ca2+ release from intracellular stores and activation of a nickel- and nifedipine-sensitive Ca2+ entry mechanism.

In a controlled crossover trial, 15 patients with frequent ventricular arrhythmias were treated with lidocaine to predict efficacy and safety of oral mexiletine. After an initial control period, patients received intravenous lidocaine (bolus infusion of 200 mg/20 min followed by 3.6 gm/24 hr and for 7 days oral mexiletine (200 mg four times a day). Efficacy was controlled by 24-hour Holter monitoring (responders = suppression of single premature ventricular beats [PVB] >84% and of complex PVB >90%). After lidocaine, 10 of 15 patients (67%) were responders (mean PVB reduction: 97%). After mexiletine, five of 15 patients (33%) were responders (mean PVB reduction: 81%); efficacy was closely related to the plasma concentration. When efficacy of both agents was compared, lidocaine infusion had a positive predictive value of only 50%; however, the negative predictive value was 100%. Thus in nonresponders to lidocaine, mexiletine is very likely to fail in the suppression of ventricular ectopy.

Objectives. The present study investigated current management strategies as well as the clinical course of acute major pulmonary embolism.

Looks at a brand-new American line of bed linens designed by Swedish-born Anki Spets, which echo Finnish and Italian textiles of 25 years ago, updated by her this-minute sense of style.

Looks at a group of rooms created by designers Mark Epstein and William McGinn that combine Laura Ashley prints with unexpected combinations of colors.

Presents a case study on urban combat in 1997 Civil War in the Republic of Congo. Outline of the political history that led to the civil war; Account of the fighting between the Cobras and Zulu militia; Evacuation operations done by foreign countries; Tactical operations employed by both militias; Weapon system of the pre-war Congolese Republic Army.

Focuses on hairstyling products. Background history; Mousses; Gels; Hair sprays; Shine products; Compliance with environmental standards.

Discusses a wide range of products offered by skin-care companies for home treatments. Advantages of having spa treatments; Disadvantages of home treatments. INSETS: Seaweed (spa home treatment).;Exfoliators (massage treatment).;Special soaks (bubble-bath products).;Massage (massage products).

The article discusses Cindy Sherman, a contemporary artist, best known for dressing up and photographing herself in self portraits and assuming the guise of Marquise de Pompadour. Sherman designs porcelain dinnerware for Artes Magnus America, based in New York City, alongside George Segal and Arman, all of whom were the first of 20 fine artists to do so. The process of transferring an image onto porcelain is very complex, requiring up to 16 photo silk screens resulting in what the author states as a visual commentary.

Profiles Princess Stephanie of Monaco. Childhood; Personal style; Family life; Beauty regimen; Goals for a singing career.

The article discusses architectural projects designed by Kohn Pedersen Fox Associates (KPF) for American Broadcasting Co. (ABC). KPF has designed a total of 14 projects for ABC, which most of it are situated on 66th and 67th Streets in New York City. KPF adopted strategies for the projects, such as the use of limestone and brick palette. Projects designed by KPF for ABC include the 1905 New York State Medical Battalion Armory that was converted to studios and Capital Cities/ABC Headquarters.

The article features the renovation done to an Upper East Side apartment in Manhattan, New York City. Designers Gisue and Mojgan Hariri reportedly drew on their fascination with the unpredictable urban patterns of Manhattan. The renovation is described as having an environment with purpose and restrained energy. Walls and windows, fixtures and materials were reportedly placed and used with precision.

The article features the renovated Altschiller Reitzfeld David Tracy-Locke (ARDT-L) Advertising Agency Office in Miss/Getchel Loft in New York City. Henry Smith-Miller and Laurie Hawkinson, who have been using programmic approach with motion in their practice, renovated the loft. Other projects completed by Smith-Miller and Hawkinson are cited.

The article describes the house in Connecticut created by Mark Simon and James C. Childress which they built based on Childress's simple but bold terms. The designers built symmetrical wings but on different angles with two brick chimneys at the entrance. The article describes a simple appearance viewed from the outside, but looking from the inside there is a feeling of greatness.

Describes the design of a New York City apartment by Brian Stoner in collaboration with John Hutton. Interior details.

Given the clinical potential of poly(ADP-ribose) polymerases (PARP) imaging for the detection and stratification of various cancers, the development of novel PARP imaging probes with improved pharmacological profiles over established PARP imaging agents is warranted. Here, we present a novel 18F-labeled PARP radiotracer based on the clinically superior PARP inhibitor talazoparib. An automated radiosynthesis of [18F]talazoparib (RCY: 13 ± 3.4%; n= 4) was achieved using a “design of experiments” (DoE) optimized copper-mediated radiofluorination reaction. The chiral product was isolated from the reaction mixture using 2D reversed-phase/chiral radio-HPLC (>99% ee). (8S,9R)-[18F]Talazoparib demonstrated PARP binding in HCC1937 cells in vitroand showed an excellent tumor-to-blood ratio in xenograft-bearing mice (10.2 ± 1.5). Additionally, a favorable pharmacological profile in terms of excretion, metabolism, and target engagement was observed. This synthesis of [18F]talazoparib exemplifies how DoE can enable the radiosyntheses of synthetically challenging radiolabeled compounds of high interest to the imaging community.

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