Heart-to-liver activity ratios measured on the anterior SPECT projections were significantly higher for tetrofosmin than for sestamibi in the rest and stress studies. Heart-to-lung ratios were similar for both tracers. Significant linear correlations between tetrofosmin and sestamibi perfusion indices were found in normals and in patients with proven or suspected coronary artery disease. In segments showing abnormal uptake during stress, the perfusion indices were similar for tetrofosmin and sestamibi at rest and during stress. The degree of reversibility in these segments was also similar for both tracers. Finally, the extent, intensity and severity of perfusion defects were similar for both tracer studies.
In the Group 1 animals, 99mTc activity (y) was related to myocardial blood flow (x) from 0 to 6.1 ml/min/g by the relationship y = 0.83X + 0.18, r = 0.95, p = 0.0001. The scintigraphic ratio of myocardial perfusion defect zone counts-to-normal myocardial zone counts (0.54 +/- 0.05 at 30 min) remained constant over 4 hr, as did technetium counts from direct endocardial sampling. Scintigraphic count ratios allowed discrimination between perfusion defect and normal myocardial regions beginning at 5 min following 99mTc-Q3 injection.
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The results obtained indicate that pelletization can be considered as a method of choice for pilot plant and/or full-scale production of controlled-release dosage forms based on the formation of amorphous solid dispersions.
As many as 24 patients suffering from essential hypertension (EH) were examined. The patients were subjected to Holter ECG monitoring, echocardiography, coronary angiography, exercise scintigraphy of the myocardium with transesophageal pacing of the atria and the dipyridamole test. The patients manifested defects of thallium accumulation during exercise scintigraphy of the myocardium. They were transitory defects of accumulation with clearance impairment recorded in EH patients with atherosclerosis of the coronary arteries; transitory defects of accumulation without clearance impairment recorded in EH patients with the angiographically unchanged coronary arteries. In Holter ECG monitoring, the patients with a silent depression of the ST segment demonstrated transitory defects of thallium accumulation by the myocardium in all the cases during exercise scintigraphy of the myocardium.
Because TMCG/DIPY treatment modulates the methylation status/stability of E2F1, the results demonstrate that therapies targeting the epigenetic machinery of cancer cells in the presence of overexpressed E2F1 may result in efficient E2F1-mediated cell death.
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Hyphosphatemia can be seen in renal transplant recipients. Hyperparathyroidism, glucocorticoid treatment, renal denervation and impairment of renal tubular phosphate reabsorption are the most common causes of hyphosphatemia in these patients. It is well-known that dipyridamole enhances renal tubular phosphate reabsorption in some clinical conditions. We did not find any information about the effect of dipyridamole in renal transplant recipients (RTRs) with hypophosphatemia. For this reason, we decided to give dipyridamole 11 RTRs with hypophosphatemia.
We have previously found that acute intravenous infusion of an ACE inhibitor normalized the reduced coronary vasomotor function in type 2 diabetes. The aim of the present study was to extend this investigation to an angiotensin II receptor blocker (ARB) administered orally in normotensive, asymptomatic type 2 diabetes patients without albuminuria.
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Kinetics for transport of adenosine into guinea-pig neocortex synaptosomes were studied by incubating them with [14C]adenosine for up to 30 s. The apparent Km value of the high-affinity transport system for adenosine was 21.1 microM and the Vmax value was 257.3 pmol/min/mg protein. The transport system was inhibited by both compounds structurally related (compounds 554 and 555) and unrelated (dipyridamole) to adenosine. Because electrically stimulated synaptosomes release up to 1.5% of the adenosine derivative content per min, the physiological significance of adenosine uptake is discussed as a possible mechanism to compensate for the loss of adenine nucleotides from synaptosomal preparations.
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Patients with hypertension frequently complain of chest pain and exhibit ischemic-like ST segment changes on the exercise electrocardiogram (ECG). However, the specificity of such changes for predicting significant CAD is very low, because these patients often exhibit a normal coronary angiogram.
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Antiplatelet agents are effective for secondary prevention after ischemic stroke, although they do not always prevent recurrent events. Laboratory studies confirm that therapy with 3 antiplatelet agents is superior to dual therapy or monotherapy at inhibiting platelet and leucocyte function. We report here a 69-year-old man who had recurrent strokes despite single or dual antiplatelet agents, but who responded to a combination of aspirin, dipyridamole, and clopidogrel. Likewise, triple antiplatelet therapy was effective in a series of 8 additional patients during a period of 28 months of follow up. Because combining 3 agents runs the risk of major bleeding, clinical trials are essential to address issues of safety and efficacy in patients with stroke.
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Experiments with isolated perfused hearts of guinea pigs and rats showed that cardiac action is linked to formation of prostaglandinlike substances (PLS) and prostacyclin (PGI2). Perfusion of the hearts with arachidonic acid or pretreatment with a linoleic-acid-supplemented diet significantly increased the content of PLS and PGI2 and exerted an economic effect on the heart performance. Dipyridamole induced a marked increase in the coronary flow and PGI2 formation of the hearts but decreased the enhanced myocardial PGI2 biosynthesis after perfusion with arachidonic acid. Propranolol also caused a rise in PGI2 efflux but did not show any influence on PGI2 formation after arachidonic acid. Dipyridamole and propranolol prevent decreased PGI2 formation after acetylsalicylic acid, supporting the view that a combination of these drugs exerts a preventive effect in patients with angina pectoris and heart infarction.
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Antiplatelet agents are often included in plasma exchange-based regimens for thrombotic thrombocytopenic purpura (TTP) patients; however, the opportuneness of their use in TTP is still controversial. The italian Cooperative Group for TTP carried out a randomized trial to investigate their actual effectiveness, both in acute TTP and as maintenance treatment.
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To estimate the prevalence of inappropriate medications prescribed by office-based physicians for patients 65 years or older.
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Ethylenediaminetetraacetic acid (EDTA) is the anticoagulant recommended for full blood counts, citrate is recommended for coagulation and platelet studies, and citrate-theophylline-adenosine-dipyridamole (CTAD) inhibits platelet activation. Because the combination of EDTA and CTAD (E/C) is better than EDTA or CTAD alone for measuring platelet parameters on the ADVIA 120 Haematology System, we investigated whether it also offers advantages for the flow cytometric assessment of platelet and/or neutrophil activation and platelet-leucocyte aggregate formation ex vivo. Blood from healthy subjects was collected into E/C or citrate, kept at room temperature or at 4 degrees C, and analysed 0 to 360 min later in the ADVIA 120 and by immunofluorescent flow cytometry. Platelet count, mean platelet volume, number of platelet clumps, mean platelet component, numbers of CD62P(+) platelets and platelet-leucocyte aggregates, and expression of CD11b on neutrophils changed little over 360 min in blood with E/C kept at 4 degrees C. In contrast, one or more parameter changed when blood was kept with E/C at ambient temperature or with citrate at either temperature. The use of E/C in in vitro and in vivo studies is illustrated. Platelet and neutrophil activation status ex vivo can be reliably assessed if blood is collected into E/C, held at 4 degrees C, and analysed within 6 h.
All 3 types of CRVO, showed a significantly greater severity of retinal hemorrhages among aspirin users than nonusers (P<0.001). Initial visual acuity and visual fields were significantly worse in aspirin users than nonusers in nonischemic CRVO and hemi-CRVO, but did not differ for ischemic CRVO. Among patients with nonischemic CRVO who initially had 20/60 or better visual acuity, there was a significant association of aspirin use with visual acuity deterioration. The odds ratio of visual acuity deterioration, adjusting for age, diabetes, ischemic heart disease, and hypertension, for aspirin users relative to nonusers was 2.24 (95% confidence interval [CI], 1.14-4.41; P = 0.020). Of those whose macular edema resolved, overall cumulative visual acuity outcome also suggested a higher percentage with deterioration among aspirin users, odds ratio for deterioration of 3.62 (95% CI, 0.97-13.54; P = 0.05) for aspirin users relative to nonusers. For the nonischemic CRVO patients with 20/70 or worse visual acuity at the initial visit, after resolution of macular edema, improvement in visual acuity was less likely in the aspirin users than in nonusers (odds ratio, 0.18; 95% CI, 0.04-0.72; P = 0.016).
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The noninvasive diagnosis of coronary artery disease in the elderly can occasionally be difficult. Intravenous dipyridamole-thallium imaging is a potentially useful diagnostic test to determine presence and severity of coronary disease; however, the safety of the procedure has not been determined in an older population. The side effect profile and frequency of severe ischemic responses after 0.56 mg/kg of intravenous dipyridamole were compared in 101 patients greater than or equal to 70 years old and 236 patients less than 70 years old. There were no side effects in 64% and 62% of patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). Among the 337 patients tested, there were no complications of myocardial infarction or death. The most common cardiac side effect was chest pain, which occurred in 21 (21%) of the 101 patients aged greater than or equal to 70 years and in 64 (27%) of the 236 patients less than 70 years (p = NS). Aminophylline was required to reverse cardiac or noncardiac side effects in 15 (15%) and 36 (15%) of the patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). A severe ischemic response occurred in 2% and 2.5% of patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). The sensitivity of intravenous dipyridamole-thallium imaging for obstructive coronary artery disease was 86% (25 of 29) and 83% (68 of 82) in older and younger patients, respectively (p = NS); the specificity was 75% (6 of 8) and 70% (16 of 23), respectively (p = NS). Thus, intravenous dipyridamole-thallium imaging is a safe noninvasive method for assessment of older patients with obstructive coronary disease; its side effect profile and diagnostic accuracy are similar to those seen in younger patients. The technique is associated with severe ischemic responses in only a small minority of patients.
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After local tissue depositioning of 133Xenon (133Xe) the regional washout is usually registered by a NaI(Tl) detector. The residual radioactivity of 133Xe is usually measured at its 81 keV photopeak. However, using small Silicon (Si) photodiodes it is feasible to measure only the low-energy activity in the X-ray energy range. In the myocardium of open chest dogs 133Xe washout measurements by a matrix of Si diodes composed in a 4 x 4 array and a conventional NaI(Tl) detector were carried out simultaneously. Fourteen separate pairs of measurements were performed in 3 dogs. When the Si-diodes in the matrix were selected individually in accordance to the position with reference to the diode with maximum count rate or pooled, comparisons could be made between the corresponding washout rate constants measured by the reference detector. In the correlation between the rate constants the intercepts with the y axis were not significantly different from zero allowing the correlation lines to be fitted through (0.0). The slope of the correlation line was close to unity. The registration of the low-X-ray energy of 133Xe by the Si-detectors is an alternative to the conventional high energy activity recording appearing from the gamma-energy of the photopeak. The detector matrix concept allows elimination of motion artefacts and indicator distribution in the myocardial tissue. Due to the uniformity and low cost of Si-diodes the perspective may be the introduction as a disposable transducer useful during cardiac surgery for example.
Clinical observations suggest that a casual relationship exists between the increased platelet aggregability and complicated migraine attacks which appear during the course of oral contraception. In the case reported the attacks continued to appear after contraception was stopped. When reduction of the platelet aggregability was noted, a decrease in the frequency of the migraine attacks, and their eventual disappearance, was seen. Studies on the subject suggest that OCs have the property of conversion of an ordinary migraine into a particularly malignant form of cerebral infarction. Additional clinical and experimental data are required to fully evaluate the problem.
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We performed a study to evaluate the effect of acetylsalicylic acid (ASA) plus dipyridamole on the retinal vascular pattern over 3 months in rats with experimental diabetes mellitus. Rats treated with ASA alone showed a continuous vascular bed and less tortuous vessels than untreated diabetic rats. Rats treated with ASA plus dipyridamole showed a continuous vascular bed, scarce tortuous vessels and vascular diameters similar to those in nondiabetic control rats. The findings were related to aortic prostacyclin production: treatment with ASA alone produced a reduction in prostacyclin production, whereas treatment with ASA plus dipyridamole resulted in normal prostacyclin production. ASA alone or with dipyridamole inhibited collagen-induced aggregation in whole blood by 57% compared with the untreated diabetic rats.
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After uncomplicated myocardial infarction, clinical and ergometric data before hospital discharge allow identification of patients at high risk of further cardiac events. These relate to the necrosed myocardium (left ventricular dysfunction, sometimes latent, and arrhythmia risk), and also to the jeopardized myocardium: the moderate sensitivity and specificity of classical exercise stress testing for the detection of this often silent ischaemia are much improved by stress radionuclide and echocardiographic techniques (exercise, dipyridamole, dobutamine. . .), the large scale indications of which remain to be validated.
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We evaluated the short-term and mid-term differences in perfusion and function after off-pump and on-pump coronary artery bypass grafting (CABG) using gated myocardial single photon emission computed tomography.
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In a randomised, double-blinded, placebo-controlled, cross-over study we measured the forearm blood flow response to the intrabrachial administration of dipyridamole in 14 healthy male subjects before and after treatment with placebo or eplerenone (50 mg bid for 8 days). The forearm blood flow during administration of dipyridamole (10, 30 and 100 µg·min(-1)·dl(-1)) was 1.63 (0.60), 2.13 (1.51) and 2.71 (1.32) ml·dl(-1)·min(-1) during placebo use, versus 2.00 (1.45), 2.68 (1.87) and 3.22 (1.94) ml·dl(-1)·min(-1) during eplerenone treatment (median (interquartile range); P = 0.51). Concomitant administration of the adenosine receptor antagonist caffeine attenuated dipyridamole-induced vasodilation to a similar extent in both groups. The forearm blood flow response to forearm ischemia, as a stimulus for increased formation of adenosine, was similar during both conditions.
1. The nerve-evoked contractions elicited by transmural electrical stimulation of mouse urinary bladders superfused in modified Krebs Ringer buffer containing 1 microM atropine plus 3.4 microM guanethidine were inhibited by adenosine (ADO) and related nucleoside analogues with the following rank order of potency: R-phenylisopropyladenosine (R-PIA) greater than cyclohexyladenosine (CHA) greater than 5'N-ethylcarboxamido adenosine (NECA) greater than ADO greater than S-phenylisopropyladenosine (S-PIA). Tissue preincubation with 8-phenyltheophylline (8-PT) displaced to the right, in a parallel fashion, the NECA concentration-response curve. 2. The contractions elicited by application of exogenous adenosine 5'-triphosphate (ATP) were also inhibited by ADO and related structural analogues. The rank order of potency to reduce the motor response to ATP was: NECA greater than 2-chloroadenosine (CADO) greater than R-PIA greater than ADO greater than CHA greater than S-PIA. 3. The ADO-induced ATP antagonism was of a non-competitive nature and was not specific. Tissue incubation with 10 microM NECA not only reduced the motor responses elicited by ATP, but also 5-hydroxytryptamine, acetylcholine and prostaglandin F2 alpha. The action of NECA was antagonized following tissue preincubation with 8-PT. The inhibitory action of NECA was not mimicked by 10 microM CHA. 4. The maximal bladder ATP contractile response was significantly increased by tissue preincubation with 5-30 microM 8-PT. 5. The 0.15 Hz evoked muscular twitch was significantly increased by 8-PT while dipyridamole consistently reduced the magnitude of the twitch response. These results are consonant with the hypothesis that an endogenous ADO tone modulates the bladder neurotransmission. 6. A working model is proposed suggesting the presence of ADO-Al and A2 receptors in the mouse urinary bladder. The A1 receptor subpopulation is probably of presynaptic origin whereas the smooth muscle membranes contain a population of the A2 receptor subtype.
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The effect of hypoxia on the release of adenosine was studied in vitro in the rat whole carotid body (CB) and compared with the effect of hypoxia (2%, 5% and 10% O(2)) on adenosine concentrations in superior cervical ganglia (SCG) and carotid arteries. Moderate hypoxia (10% O(2)) increased adenosine concentrations released from the CBs by 44%, but was not a strong enough stimulus to evoke adenosine release from SCG and arterial tissue. The extracellular pathways of adenosine production in rat CBs in normoxia and hypoxia were also investigated. S-(p-nitrobenzyl)-6-thioinosine (NBTI) and dipyridamole were used as pharmacological tools to inhibit adenosine equilibrative transporters (ENT) and alpha,beta-methylene ADP (AOPCP) to inhibit ecto-5'-nucleotidase. Approximately 40% of extracellular adenosine in the CB came from the extracellular catabolism of ATP, under both normoxic and hypoxic conditions. Low pO(2) triggers adenosine efflux through activation of NBTI-sensitive ENT. This effect was only apparent in hypoxia and when adenosine extracellular concentrations were reduced by the blockade of ecto-5'-nucleotidase. We concluded that CB chemoreceptor sensitivity could be related to its low threshold for the release of adenosine in response to hypoxia here quantified for the first time.
The specific P1-purinoceptor agonist 2-chloroadenosine (3 X 10(-7) M to 3 X 10(-6) M) reduced the magnitude of excitatory junction potentials (e.j.p.s) recorded from guinea-pig vas deferens in response to field stimulation of the sympathetic nerves, but did not have any direct effect on the resting membrane potential. Trains of pulses (2-16 Hz) for 20 s produced a biphasic contractile response, both phases of which were reduced by 2-chloroadenosine (10(-7) to 10(-5) M) by up to 45%. In contrast, the same concentrations of 2-chloroadenosine enhanced by about 20% the contractile response of the vas deferens to exogenously applied adenosine 5'-triphosphate (ATP) and noradrenaline (NA). The specific P1-purinoceptor antagonist 8-phenyltheophylline (8-PT) reversed the inhibitory effect of 2-chloroadenosine on e.j.p. magnitude, partially reversed the inhibitory action of 2-chloroadenosine on both phases of the contractile response to nerve stimulation, and partially reversed the enhancing effect of 2-chloroadenosine on responses to exogenous ATP and NA. We propose that release of ATP and NA (as cotransmitters) from sympathetic nerves can be modulated by prejunctional P1-purinoceptors.
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To validate coronary sinus flow measurements for quantification of global left ventricular (LV) perfusion by means of velocity-encoded cine (VEC) magnetic resonance (MR) imaging and flow probes.
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CFR is inversely related to the number of conventional risk factors in patients with 1-vessel CAD and intermediate coronary artery stenosis, whereas this influence is less evident in patients with more severe stenosis.
Dentists making management decisions regarding patients taking antiplatelet therapy should consider the patient's risk of experiencing perioperative hemorrhage against the risk of experiencing complications associated with thromboembolic events. The risk of perioperative bleeding complications is low for patients taking single or dual antiplatelet therapy. Intraoperative and postoperative bleeding can be controlled with local hemostatic measures.
The coronary angiography provides information on the anatomical state of the coronary tree, while myocardial perfusion scintigraphy (MPI) facilitates the evaluation of the grade of ischaemia that a particular stenosis produces. The purpose of MPI is to detect the coronary stenosis that provokes the ischaemia and is termed the "culprit lesion". The aim of this study was to evaluate the accuracy of 1-day DypEX 99mTc-tetrofosmin tomography in the identification and localization of culprit lesion in the patients with known coronary artery disease (CAD).
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Insulin resistance is a metabolic spectrum that progresses from hyperinsulinemia to the metabolic syndrome, impaired glucose tolerance, and finally type 2 diabetes mellitus. It is unclear when vascular abnormalities begin in this spectrum of metabolic effects.