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21.
A ‘crazy-paving’ appearance of the lungs on computed tomography scanning of the chest was first described nearly 20 years ago in patients with pulmonary alveolar proteinosis, and was thought to be characteristic of this condition. However, this pattern has subsequently been reported in a variety of pulmonary diseases and is now considered to be nonspecific. The present report describes a case of a 74-year-old man in whom congestive heart failure presented with a crazy-paving appearance of the lungs on a chest computed tomography scan. This uncommon association illustrates the importance of the correlation of clinical and radiographic information. 相似文献
22.
23.
Jacqueline AM Smith DL Patil OT Daniels Y-S Ding J-D Gallezot S Henry KHS Kim S Kshirsagar WJ Martin GP Obedencio E Stangeland PR Tsuruda W Williams RE Carson ST Patil 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2015,18(2)
Background:
Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters.Methods:
We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.Results:
TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC50 of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo.Accounting for species differences in protein binding, the projected human NET and SERT plasma EC50 values were 5.5ng/mL and 23.9ng/mL, respectively. A single-dose, open-label PET study (4–20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [11C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [11C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30–40h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC50 for NET was estimated to be 1.21ng/mL, and at doses of greater than 4mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35ng/mL.Conclusions:
These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation. 相似文献24.
Opening of ATP-sensitive potassium channels causes generation of free radicals in vascular smooth muscle cells 总被引:4,自引:2,他引:4
Krenz M Oldenburg O Wimpee H Cohen MV Garlid KD Critz SD Downey JM Benoit JN 《Basic research in cardiology》2002,97(5):365-373
Recent evidence suggests that opening of mitochondrial KATP channels in cardiac muscle triggers the preconditioning phenomenon through free radical production. The present study tested
the effects of KATP channel openers in a vascular smooth muscle cell model using the fluorescent probe MitoTracker (MTR) Red™ for detection of
reactive oxygen species (ROS). Rat aortic smooth muscle cells (A7r5) were incubated with 1 μM reduced MTR (non-fluorescent)
and the MTR oxidation product (fluorescent) was quantified. Thirty-minute pretreatment with either diazoxide (200 μM) or pinacidil
(100 μM), both potent mitochondrial KATP channel openers, increased fluorescent intensity (FI) to 149 and 162 % of control (p < 0.05 for both), respectively, and
the KATP channel inhibitor 5-hydroxydecanoate (5HD) blocked it. Valinomycin, a potassium-selective ionophore, raised FI to 156 % of
control (p <: 0.05). However, 5HD did not affect the valinomycin-induced increase in FI. Inhibition of mitochondrial electron
transport (myxothiazol) or uncoupling of oxidative phosphorylation (dinitrophenol) also blocked either valinomycin- or diazoxide-induced
increase in FI, and free radical scavengers prevented any diazoxide-mediated increase in fluorescence. Finally the diazoxide-induced
increase in fluorescence was not blocked by the PKC inhibitor chelerythrine, but was by HMR 1883, a putative surface KATP channel blocker. Thus opening of KATP channels increases generation of ROS via the mitochondrial electron transport chain in vascular smooth muscle cells. Furthermore,
a potassium-selective ionophore can mimic the effect of putative mitochondrial KATP channel openers. We conclude that potassium
movement through KATP directly leads to ROS production by the mitochondria.
Received: 7 January 2002, Returned for revision: 31 January 2002, Revision received: 21 February 2002, Accepted: 14 March
2002 相似文献
25.
High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy 总被引:2,自引:1,他引:2
Brown RA; Herzig RH; Wolff SN; Frei-Lahr D; Pineiro L; Bolwell BJ; Lowder JN; Harden EA; Hande KR; Herzig GP 《Blood》1990,76(3):473-479
Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens. 相似文献
26.
Seelwan Sathitratanacheewin Ruth A. Engelberg Lois Downey Robert Y. Lee James A. Fausto Helene Starks Ben Dunlap James Sibley William Lober Elizabeth T. Loggers Nita Khandelwal J. Randall Curtis 《Journal of pain and symptom management》2018,55(1):75-81
Context
Recent analyses of Medicare data show decreases over time in intensity of end-of-life care. Few studies exist regarding trends in intensity of end-of-life care for those under 65 years of age.Objectives
To examine recent temporal trends in place of death, and both hospital and intensive care unit (ICU) utilization, for age-stratified decedents with chronic, life-limiting diagnoses (<65 vs. ≥65 years) who received care in a large healthcare system.Methods
Retrospective cohort using death certificates and electronic health records for 22,068 patients with chronic illnesses who died between 2010 and 2015. We examined utilization overall and stratified by age using multiple regression.Results
The proportion of deaths at home did not change, but hospital admissions in the last 30 days of life decreased significantly from 2010 to 2015 (hospital b = ?0.026; CI = ?0.041, ?0.012). ICU admissions in the last 30 days also declined over time for the full sample and for patients aged 65 years or older (overall b = ?0.023; CI = ?0.039, ?0.007), but was not significant for younger decedents. Length of stay (LOS) did not decrease for those using the hospital or ICU.Conclusion
From 2010 to 2015, we observed a decrease in hospital admissions for all age groups and in ICU admissions for those over 65 years. As there were no changes in the proportion of patients with chronic illness who died at home nor in hospital or ICU LOS in the last 30 days, hospital and ICU admissions in the last 30 days may be a more responsive quality metric than site of death or LOS for palliative care interventions. 相似文献27.
28.
Reduced memory skills and increased hair cortisol levels in recent Ecstasy/MDMA users: significant but independent neurocognitive and neurohormonal deficits 下载免费PDF全文
29.
Summary The relationship between the blood flow pattern immediately following coronary artery occlusion and the resulting infarct 24 hours later was studied in dogs treated with isoproterenol (0.5 g/kg/min for 2 hours) or with propranolol (2mg/kg every 6 hours). The coronary artery of a closed chest dog was perfused via a special cannula with arterial blood. A 2-mm diameter plastic bead was introduced into the perfusate to embolize a coronary branch. One minute after occlusion, radiolabelled microspheres were injected into the perfusate. The dogs were then allowed to recover. 24 hours later the dogs were reanesthetized and their hearts removed. The hearts were sliced into 4 mm thick sections and the microsphere distribution was visualized by autoradiography of the tissue. Superimposition of developed autoradiographs and tracings of the infarct pattern of stained sections allowed direct comparison of the blood flow pattern immediately after occlusion to the eventual pattern of infarction. In all 8 control dogs, all 6 isoproterenol dogs and all 12 propranolol dogs the lateral borders of blood flow and infarction were superimposable indicating no lateral change in infarct size resulting from treatment. In the control group there was a subepicardial region of the ischemic zone which did not infarct (15.2±2.3% of the ischemic zone). Though isoproterenol did not significantly change the size of this zone, propranolol increased it to 35.9±6,5% (p<0.005) indicating vertical but not lateral salvage.Supported by Grant HL-20648 from NIH: HLBI and a Grant-in-aid from the American Heart Association and with funds contributed in part by the Northwest Ohio Chapter, Inc. 相似文献
30.
It has been assumed that all G(i)-coupled receptors trigger the protective action of preconditioning by means of an identical intracellular signaling pathway. To test this assumption, rabbit hearts were isolated and perfused with Krebs buffer. All hearts were subjected to a 30-minute coronary artery occlusion followed by 120 minutes of reperfusion. Risk area was measured with fluorescent particles and infarct size with triphenyltetrazolium chloride staining. Control hearts showed 29.1+/-2.8% infarction of the risk zone. A 5-minute infusion of acetylcholine (0.55 mmol/L) beginning 15 minutes before the 30-minute occlusion resulted in significant protection (9.2+/-2.7% infarction). This protection could be blocked by administration of 300 micromol/L N-2-mercaptopropionyl glycine (MPG), a free radical scavenger, or by 200 micromol/L 5-hydroxydecanoate (5-HD), a mitochondrial K(ATP) antagonist, for 15 minutes beginning 5 minutes before the acetylcholine infusion (35.2+/-3.9% and 27.8+/-2.4% infarction, respectively). Similar protection was observed with other known triggers, ie, bradykinin (0.4 micromol/L), morphine (0.3 micromol/L), and phenylephrine (0.1 micromol/L), and in each case protection was completely abrogated by either MPG or 5-HD. In contrast, protection by adenosine or its analog N(6)-(2-phenylisopropyl) adenosine could not be blocked by either MPG or 5-HD. Therefore, whereas most of the tested agonists trigger protection by a pathway that requires opening of mitochondrial K(ATP) channels and production of free radicals, the protective action of adenosine is not dependent on either of these steps. Hence, it cannot be assumed that all G(i)-coupled receptors use the same signal transduction pathways to trigger preconditioning. 相似文献