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Biomedical subjects

M Chiariello

Publications and source records attributed to M Chiariello.

At least 91 records · Page 5Linked to original sources
PubMed1997

In vivo gene transfer: prevention of neointima formation by inhibition of mitogen-activated protein kinase kinase.

BACKGROUND: The mitogen-activated protein kinase kinase (MAPKK) is a protein downstream ras which is rapidly activated in cells stimulated with various extracellular signals. These proteins are believed to play a pivotal role in integrating and transmitting transmembrane signals required for cell growth. METHODS AND RESULTS: To study the effect of inhibition of MAPKK on smooth muscle cell (SMC) proliferation in vivo after vascular injury, we performed experimental balloon angioplasty using the standard Clowes technique in male Wistar rats 14-weeks old. The animals did not receive any treatment after vascular injury (N = 6) or were randomly assigned to receive, after balloon injury, a 30% (w/v) pluronic gel solution applied to the injured carotid artery, containing respectively: 1) no plasmid DNA (n = 10); 2) RSV-lacZ (encoding the beta-galactosidase gene) as control gene without effects on SMC proliferation (n = 10); 3) Tg-CAT (encoding cloramphenicol acetyl-transferase gene under the control of thyreoglobulin promoter) as an additional control gene without effects on SMC proliferation (n = 7): 4) a negative mutant of Mitogen-Activated Protein Kinase Kinase (MAPKK-) (n = 13). Fourteen days after vascular injury, carotid arteries were removed and cross sections were cut and stained with hematoxylin/eosin. Morphometric analysis demonstrated, in the MAPKK- treated rats, a significant reduction of both neointima (0.096+/-.018 mm2 vs. 0.184+/-0.019 mm2, p < 0.01) and neointima/media ratio (0.603+/-0.103 vs. 1.471+/-0.161, p < 0.01) compared to control DNA. CONCLUSIONS: The inhibition of MAPKK, by a dominant inhibitor mutant gene, prevents the SMC proliferation after vascular injury in vivo.

Animals↗
PubMed1997

Glycosylation enhances oxygen radical-induced modifications and decreases acetylhydrolase activity of human low density lipoprotein.

BACKGROUND: Posttranslational nonenzymatic glycosylation of native low-density lipoprotein (n-LDL) occurs both in vitro and in vivo in diabetic patients. Glycosylated LDL (glc-LDL) behave similarly to oxidized LDL in some respects. In fact, unlike n-LDL, uptake the glc-LDL can occur in part by the "scavenger" receptor(s), as also demonstrated for oxidized LDL. The enzyme acetylhydrolase, carried by LDL, catabolizes platelet activating factor (PAF). This enzymatic activity is inhibited in oxidized LDL. However, it is unknown whether glc-LDL have reduced acetylhydrolase activity. OBJECTIVE: The first aim of the study was to investigate whether glc-LDL were more susceptible than n-LDL to oxidative modification, and which different oxygen radical species were involved in the phenomenon. Moreover, in order to investigate whether glycosylation may affect acetylhydrolase, we also measured this enzymatic activity in both n- and glc-LDL. METHODS: In vitro glc-LDL and n-LDL were exposed to the oxidants xanthine/xanthine oxidase (X/XO; 2 mM and 100 mU/ml, respectively), or CuSO4 (10 microM) for 18 hs at 37 degrees C. Parallel experiments were done in the presence of the superoxide radical scavenger superoxide dismutase (SOD; 330 U/ml), the hydrogen peroxide scavenger catalase (1000 U/ml), or the hydroxyl radical scavenger dimethylthiourea (10 mM) or dimethylsulfoxide (1 mM). Standards of PAF and lyso-PAF were visualized with iodine vapors after separation by thin layer chromatography. The distribution of label was determined by an imaging scanner. Labeled products were then isolated from the chromatography plate, and the amount of 3H-lyso-PAF formed was determined by liquid scintillation counting. RESULTS: Glc-LDL were more susceptible than n-LDL to lipid peroxidation (n-LDL 22.9 +/- 3.4 vs 34.8 +/- 4.2* nmoles/MDA/mg of protein in glc-LDL oxidized by X/XO and n-LDL 28.9 +/- 4.2 vs 40.4 +/- 4.1* in glc-LDL oxidized by CuSO4, *p < 0.05 vs n-LDL). SOD, but not other scavengers, prevented peroxidation, indicating an obligatory role for superoxide radicals. Oxidation of glc-LDL also induced a higher degree of apolipoprotein-B100 modifications than n-LDL, with increased electrophoresis mobility and decreased TNBS reactivity. These effects were similarly prevented by SOD. Finally, acetylhydrolase activity was significantly lower in glc-LDL than in n-LDL. CONCLUSION: Glycosylation increases LDL oxidation due to superoxide radicals, and also reduces acetylhydrolase activity. These phenomenona may contribute to enhance and/or accelerate the progression of atherosclerosis in diabetic patients.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Heart rate variability in patients with hypertrophic cardiomyopathy: association with clinical and echocardiographic features.

Autonomic dysfunction has been reported in patients with hypertrophic cardiomyopathy. To evaluate the influence of different clinical and echocardiographic features of the disease on sympathovagal balance, as assessed by heart rate variability, 33 patients with hypertrophic cardiomyopathy and 33 healthy volunteers underwent echocardiographic examination and 24-hour electrocardiogram Holter recording. Measures of vagal modulation of heart rate were lower in patients with hypertrophic cardiomyopathy than in controls, particularly in those exhibiting syncope, exertional chest pain, dyspnea, or moderate or severe mitral regurgitation. Furthermore, the age-corrected multiple regression analysis showed that the parasympathetic cardiac control was inversely related to left atrial dimension and directly related to left ventricular end-systolic dimension. Therefore in hypertrophic cardiomyopathy the parasympathetic withdrawal is more evident in patients with symptoms than in those without; the reduction in left ventricular end-systolic dimension and the increase in left atrial size are the echocardiographic features that most influence the sympathovagal balance.

Adolescent↗
PubMed1997

Decreased low-density lipoprotein oxidation after repeated selective apheresis in homozygous familial hypercholesterolemia.

Familial hypercholesterolemia was the first genetic disorder recognized to cause myocardial infarction. Patients with homozygous familial hypercholesterolemia have rapidly progressive coronary atherosclerosis with angina pectoris, myocardial infarction, or sudden death at a young age. Selective apheresis on dextran sulfate cellulose columns reduces mortality and may induce regression of coronary lesions. These patients have both increased levels and prolonged circulation residence time of low-density lipoprotein (LDL), which is not removed by cellular receptor. LDL oxidation may play a pivotal role in atherogenesis. LDL undergoes oxidation before being taken up by macrophages and then transformed into arterial wall foam cells. The aim of this study was to investigate LDL oxidation in eight homozygous patients with familial hypercholesterolemia during repeated LDL apheresis. LDL lipid peroxidation, estimated by conjugated-diene absorbance at 234 nm, lipid peroxides, and malondialdehyde showed an increased resistance against oxidation after repeated LDL apheresis. This phenomenon was also observed in the oxidative indexes of protein moiety of LDL (apolipoprotein-B100 fragmentation, trinitrobenzenesulfonic acid reactivity, and electrophoresis agarose mobility). Similarly, cholesteryl esterification was decreased after LDL apheresis. Thus selective LDL apheresis not only decreases the pool of LDL, but it also induces changes that render LDL less susceptible to oxidation. This phenomenon might contribute to reduce coronary atherosclerosis and thus mortality of these particular patients.

Apolipoprotein B-100↗
PubMed1997

Age dependency of left ventricular diastolic function in pressure overload hypertrophy.

OBJECTIVES: We sought to evaluate whether age is a determinant of left ventricular (LV) pressure overload hypertrophy and whether diastolic function influenced the aging process. BACKGROUND: The adaptation of the left ventricle to chronic pressure overload is a complex process of hormonal, structural and hemodynamic factors. Different responses in the elderly patients have been described. METHODS: LV biplane cineangiography, micromanometry and endomyocardial biopsies were carried out in 57 patients with pure or predominant aortic stenosis. Patients were classified into a senior (< 60 years, mean age +/- SD 46 +/- 10 years, n = 35) and an elderly (< 65 years; mean age 70 +/- 4 years, n = 22) study group. LV systolic function was evaluated from biplane ejection fraction and midwall fractional shortening, whereas diastolic function was assessed from the time constant of LV pressure decay, peak filling rate and the constant of myocardial stiffness. Biopsy samples were examined morphometrically for interstitial fibrosis, fibrous content, muscle fiber diameter and volume fraction of myofibrils. RESULTS: Gender distribution and the severity of aortic stenosis were comparable in the two patient groups. LV peak systolic and end-diastolic pressures were significantly higher in the elderly than in the senior group. LV ejection fraction and midwall fractional shortening were comparable in the two groups. The time constant of relaxation and the myocardial stiffness constant were greater in the elderly than in the senior group whereas the early peak filling rate was significantly reduced in the elderly group. Interstitial fibrosis was increased, although not significantly (p < 0.06), and fibrous content was enhanced (p < 0.001) in elderly patients with respect to the senior group. There was a linear correlation between age and myocardial stiffness (r = 0.55), p < 0.0001) and an inverse relation between age and early peak filling rate (r = 0.52, p < 0.0001). CONCLUSIONS: In the presence of a comparable degree of aortic valve stenosis, elderly patients (> 65 years) present with more severe LV hypertrophy than do senior patients (< 60 years). Therefore elderly patients have a more pronounced impairment of LV diastolic function, whereas systolic function is preserved. Thus, there is an age dependency of LV pressure overload hypertrophy that can be explained by the longer duration of pressure overload or an exhaustion of the adaptation process in the elderly.

Adaptation, Physiological↗
PubMed1997

Activation of cAMP-PKA signaling in vivo inhibits smooth muscle cell proliferation induced by vascular injury.

Injury of the arterial wall induces the formation of the neointima. This structure is generated by the growth of mitogenically activated smooth muscle cells of the arterial wall. The molecular mechanism underlying the formation of the neointima involves deregulated cell growth, primarily triggered by the injury of the arterial wall. The activated gene products transmitting the injury-induced mitogenic stimuli have been identified and inhibited by several means: transdominant negative expression vectors, antisense oligodeoxynucleotides, adenovirus-mediated gene transfer, antibodies and inactivating drugs. Results of our study show that local administration of 3',5'-cyclic AMP and phosphodiesterase-inhibitor drugs (aminophylline and amrinone) to rats markedly inhibits neointima formation after balloon injury in vivo and in smooth muscle cells in vitro. The growth inhibitory effect of aminophylline was completely reversed by the inhibition of cAMP-dependent protein kinase A (PKA). These findings indicate an alternative approach to the treatment of diseases associated with injury-induced cell growth of the arterial wall, as stimulation of cAMP signaling is pharmacologically feasible in the clinical setting.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Effects of high-cholesterol and atherogenic diets on vascular relaxation in spontaneously hypertensive rats.

Hypercholesterolemia is associated with more rapid development of atherosclerosis, and hypertension is frequently associated with abnormal vascular function. Therefore, to investigate the role of hypercholesterolemia and hypertension on vascular function, we studied three groups of male rats (aged 6 wk): normotensive Wistar-Kyoto rats (WKY) as a control group and spontaneously hypertensive rats (SHR) receiving either standard diet (SD; SHR-SD) or high-cholesterol (1%) diet (ChD; SHR-ChD). Vascular reactivity was tested on isolated aortic rings at 4 wk and at 3 and 6 mo of diet. At 3 mo, endothelium-dependent relaxation to acetylcholine (ACh) and ADP was significantly reduced in SHR-ChD but not in SHR-SD compared with WKY. At 6 mo, relaxations to ACh were further impaired in both SHR groups compared with WKY. Endothelium-independent vasodilation to nitroglycerin (NTG) was not different in the three groups of animals throughout 6 mo of diet. In additional experiments, we evaluated vascular reactivity in rats fed with ChD enriched with an excess of vitamin D [atherogenic diet (AD)] capable of producing vascular atherosclerotic lesions. In particular, we studied three additional groups of WKY and SHR rats fed with SD, AD, or AD plus a nonhypotensive dose of the calcium antagonist nitrendipine (Nit). Vasodilation to ACh and ADP was significantly blunted in WKY-AD compared with WKY-SD, whereas it was partially improved in WKY-Nit. There were no differences in endothelium-independent relaxation to NTG in the three WKY groups. In contrast, SHR-AD showed a marked reduction of endothelium-dependent and -independent vasodilation, but only endothelium-dependent vasodilation was preserved by addition of Nit to the diet. These data suggest that the development of vascular dysfunction in rat genetic hypertension is accelerated by ChD, in absence of detectable vascular lesions. Our study also shows that AD alters both vascular smooth muscle and endothelium-dependent relaxation. Low doses of Nit partially preserve endothelium-dependent vasodilation but do not affect the impairment of smooth muscle function in these rats.

Animals↗
PubMed1997

Ceruloplasmin impairs endothelium-dependent relaxation of rabbit aorta.

This study evaluated the effects of ceruloplasmin, the copper-containing blue oxidase of vertebrate plasma, on the relaxation of rabbit aortic rings after endothelial release of nitric oxide (NO). Ceruloplasmin at physiological, i.e., micromolar, concentrations inhibited relaxation of rabbit aorta induced by endothelium-dependent agonists like acetylcholine or ADP, whereas it was ineffective toward vasodilation due to direct stimulation of smooth muscle cells by nitroglycerin. The effect was reversible and specific for native, fully metalated ceruloplasmin, since relaxation was not impaired by the heat-treated or metal-depleted derivatives. A trapping mechanism, involving a direct interaction of NO or other NO-containing species (like nitrosothiols and iron-dinitrosyls) with the copper sites and/or with the free thiol of ceruloplasmin, could be safely excluded on the basis of spectroscopic and chemical analyses of the protein exposed to authentic NO, nitrosothiols, or iron-dinitrosyls. The data presented in this paper constitute the first evidence of impairment of the endothelium-dependent vasodilatation by a plasma protein and may shed some light on the still uncertain physiological role of ceruloplasmin.

Acetylcholine↗
PubMed1997

Oxygen radicals can induce preconditioning in rabbit hearts.

Indirect evidence suggests that oxygen radicals may contribute to ischemic preconditioning. We directly investigated whether exposure to oxygen radicals per se, in the absence of ischemia, could reproduce the beneficial effects of ischemic preconditioning on infarct size and on postischemic contractile dysfunction. In one branch of the study, isolated rabbit hearts underwent 30 minutes of total global ischemia and 45 minutes of reperfusion (n=6, control group). A second group, before ischemia/reperfusion, was exposed for 5 minutes to a low flux of oxygen radicals generated by purine/xanthine oxidase (P/XO), followed by a 15-minute washout (n=6). Oxygen radical pretreatment significantly improved postischemic recovery of contractile function. We then investigated in another branch of the study whether this preconditioning effect would also reduce infarct size and whether it was mediated by protein kinase C activation. Control hearts were subjected to coronary artery occlusion for 30 minutes, followed by 2.5 hours of reperfusion (n=6). A second group, before coronary occlusion, was exposed to oxygen radicals and washout as described (n=8). A third group was subjected to oxygen radical infusion, but an inhibitor of protein kinase C (polymyxin B, 50 micromol/L) was administered throughout subsequent ischemia (n=7). A fourth group was exposed to oxygen radicals in the presence of scavengers (superoxide dismutase, 250 U/mL; catalase 500, U/mL; n=8). Pretreatment with oxygen radicals markedly reduced infarct size, from 65+/-19% of risk region in controls to 12+/-4% (P<.05). Protein kinase C inhibition significantly attenuated this effect (infarct size, 37+/-9% of risk region; P<.05 versus P/XO; P=NS versus controls). Oxygen radical-induced preconditioning was prevented by scavengers (infarct size, 55+/-14% of risk region; P<.05 versus P/XO; P=NS versus P/XO+polymyxin B). Our data show that in the absence of ischemia, exposure to low concentrations of oxygen radicals can reproduce the beneficial effects of ischemic preconditioning on infarct size and postischemic recovery of left ventricular function. Thus, oxygen radicals might be potential contributors to ischemic preconditioning.

Analysis of Variance↗
PubMed1997

Long-term Treatment With Pravastatin Alone and in Combination With Gemfibrozil in Familial Type IIB Hyperlipoproteinemia or Combined Hyperlipidemia.

BACKGROUND: Pravastatin inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase. It prevents mevalonate synthesis, reducing endogenous cholesterol production, and reduces cholesterol content in the liver, thus resulting in a down-regulation of low-density lipoprotein receptor production. Gemfibrozil reduces very low-density lipoprotein production and low-density lipoprotein-cholesterol level and increases very low-density lipoprotein catabolism. Therefore, it was suggested that combination therapy with both drugs could effect greater reduction of cholesterol levels as compared to pravastatin alone. The present study was carried out to evaluate the efficacy and safety of pravastatin as a monotherapy or in combination with gemfibrozil in the treatment of patients with familial type IIb hyperlipoproteinemia or familial combined hyperlipidemia. METHODS AND RESULTS: Forty-one patients were included in the study. All patients initially followed 6 weeks of hypolipidemic diet; subsequently they were randomized and received either 20 mg once daily of pravastatin alone (n = 13) or 20 mg of pravastatin together with 600 mg of gemfibrozil twice daily (n = 14). As a control, 14 patients were treated with diet only. The treatment lasted 24 months and clinical evaluation and laboratory tests were done at given time points. Both groups of treated patients showed an early reduction (3 months) of total (about 30% P <.01 vs controls), low-density lipoprotein (about 35%, P <.01 vs controls) and very low-density lipoprotein cholesterol levels (about 18%, P = NS). In contrast, high-density lipoprotein cholesterol levels increased significantly in patients treated with pravastatin and gemfibrozil (about 20%, P <.05 vs controls). Pravastatin treatment alone reduced the level of serum triglycerides as efficiently as in combination with gemfibrozil. Data showed a sustained normalization of lipid profile until 24 months. However, this effect was achieved in patients that had rather low levels of triglycerides. During the treatment we did not observe any difference in the incidence of possible drug-related side effects. Severe myopathy or rhabdomyolysis was not observed at the doses of the drugs used in our study. CONCLUSIONS: Therapy with pravastatin and in combination with gemfibrozil resulted in significant and sustained normalization of lipid profile in high-risk patients with familial type IIb hyperlipoproteinemia or familial combined hyperlipidemia.

Journal Article↗
PubMed1997

Inhibition of leucocyte and platelet adhesion reduces neointimal hyperplasia after arterial injury.

Restenosis following coronary angioplasty is though to result from migration and proliferation of medial smooth muscle cells. However, the factors that initiate this proliferation are still unknown. In a rabbit model of carotid artery injury, we tested the hypothesis that activated platelets and leucocytes might contribute to the development of neointimal hyperplasia. Following arterial injury, rabbits received either no treatment, R15.7, a monoclonal antibody against the leucocyte CD11/CD18 adhesion complex, aurintricarboxylic acid (ATA), a substance that inhibits platelet glycoprotein Ib-von Willebrand factor interaction, or the combination of R15.7 and ATA. After 21 days, the extent of neointimal hyperplasia was evaluated by planimetry on histological arterial sections. The area of neointima averaged 0.51 +/- 0.07 mm2 in control animals and it was significantly reduced by administration of either R15.7 or ATA alone to 0.12 +/- 0.05 and 0.20 +/- 0.01 mm2, respectively (p < 0.05 vs controls for both groups). The animals that received the combination of R15.7 and ATA showed a further reduction in neointimal hyperplasia, as compared to animals that received ATA alone (p < 0.05 vs ATA alone). These data indicate that platelets and leucocytes play an important role in the pathophysiology of neointimal hyperplasia in this experimental model. Interventions that reduce platelet and leucocyte adhesion to vessel wall might have beneficial effects in reducing restenosis following coronary angioplasty.

Animals↗
PubMed1997

[Cardiac performance during insulin clamp: its evaluation by bioimpedance measurement].

Ten patients with dilated cardiomyopathy, 7 ischemic heart disease and 3 idiopathic (7 males and 3 females, mean age 54.8 +/- 11 years), were studied. An insulin euglycemic clamp was performed to evaluate the influence of insulin infusion on cardiac performance. All the subjects were in NYHA functional class II-III and had an ejection fraction < 60% at a previous echocardiographic examination. They were submitted to a noninvasive continuous cardiac output monitoring by variations of thoracic impedance at three stops: a basal evaluation (T0); 1.2 mU/kg/min insulin infusion (T1); 5 mU/kg/min insulin infusion (T2). Moreover at the same times Na+, K+, hematocrit (Hct) and catecholamines were measured in the plasma. The total time required for the study was about 4 hours. Cardiac performance improved as shown by a significant increase in T1 and T2 with respect to the basal condition (T0), of ejection fraction: 57.87 +/- 11.3% (T1) vs 52.25 +/- 14.1% (T0; p < 0.01); 59.5 +/- 10.7% (T2) vs 52.25 +/- 14.1% (T0; p < 0.005); stroke volume: 2.61 +/- 0.5 l/min/m2 (T1) vs 2.01 +/- 0.75 l/min/m2 (T0; p < 0.001); 3.35 +/- 0.66 l/min/m2 (T2) vs 2.01 +/- 0.75 l/min/m2 (T0; p < 0.001) and cardiac output: 41.14 +/- 9.1 ml/m2 (T1) vs 38.83 +/- 7.1 ml/m2 (T0; p < 0.01); 46.45 +/- 8.56 ml/m2 (T2) vs 38.83 +/- 7.1 ml/m2 (T0; p < 0.001). This improvement in cardiac function was not due to an increase in preload because end diastolic volume, Hct, Na+ did not differ through the study. Similarly, afterload measured as mean blood pressure did not decrease. Cardiac function improvement was obtained in the presence of increased catecholamines. In conclusion, exogenous insulin infusion was able, in the presence of euglycemic condition, to improve cardiac performance. This improvement could be due to a direct inotropic effect of insulin perhaps mediated by its metabolic properties on cardiac muscular cells and/or by increasing the cellular intake of Ca+2.

Adult↗
PubMed1997

Laparoscopic inguinal hernioplasty: a community hospital's experience.

Although controversial, laparoscopic inguinal hernia repair has become increasingly popular among surgeons. The overall advantages of this procedure over conventional hernia repair have not as yet been substantiated. One hundred and three consecutive laparoscopic, transabdominal, preperitoneal inguinal hernia repairs in 91 patients were evaluated retrospectively. Patients' satisfaction was assessed using the Visick grading system. The mean follow-up was 18.3 months. One case was converted to an open procedure. Eighty-eight patients (91%) were discharged on the day of surgery. Eighty-seven patients (96%) were satisfied with the operation (Visick grades I & II). Twenty-nine patients who previously underwent a traditional open herniorraphy stated that they would have preferred the laparoscopic method if they had the choice. Early complications included wound infection (n = 1), urinary retention (n = 1) and intestinal obstruction necessitating a laparotomy (n = 1). All patients were ambulating without significant pain after a mean of 7.6 days, and returned to work after 2.4 weeks on average. There was one case of recurrence. In conclusion, patients are satisfied with the laparoscopic hernioplasty technique, which is associated with a low morbidity and short term recurrence rate. Laparoscopic hernioplasty should be considered a viable and valuable alternative to the open method. It appears especially attractive for recurrent or bilateral hernias.

Adult↗
PubMed1997

[Evaluation of left ventricular function in patients with mammary carcinoma after treatment with epidoxorubicin using a high-dose, short-term protocol].

Anthracyclines are effective chemotherapeutic agents against various malignancies but their therapeutic value is limited by well-known dose-related cardiotoxicity, mainly induced by oxygen free radicals. Left ventricular diastolic and systolic functional abnormalities precede the clinical evidence of cardiotoxicity. The aim of this study was to evaluate the possible cardiotoxicity of epidoxorubicin administered as "high-dose short-term" protocol. Twenty patients (mean age 50.4 +/- 7.9 years) without cardiac disease, affected by advanced breast cancer were studied. All patients were treated with epidoxorubicin as neoadjuvant chemotherapy according to the new protocol "high-dose short-term" (cumulative dose 475.8 +/- 35.6 mg/m2, range 450-600 mg/m2, in 4-6 weeks). The effectiveness of cancer chemotherapy was monitored by clinical evaluation and mammography performed before and after treatment. All patients underwent color Doppler echocardiography and resting radionuclide angiocardiography in baseline condition and 30 +/- 10 days after the last cycle of chemotherapy. All patients showed a significant reduction of tumor lesion after chemotherapy. Left ventricular systolic and diastolic function parameters obtained by echocardiography (fractional shortening 33.1 +/- 4.5% vs 32.4 +/- 4.8%; ejection fraction 63.6 +/- 6.2% vs 62.9 +/- 5.7%; E/A ratio 1.73 +/- 0.64 vs 1.82 +/- 0.67; E wave deceleration time 204 +/- 24.6 ms vs 208.5 +/- 31.7 ms;isovolumetric relaxation time 79 +/- 15.7 ms vs 80 +/- 17.8 ms) and radionuclide angiocardiography (ejection fraction 62.4 +/- 7% vs 61.8 +/- 5.9; peak ejection rate 2.87 +/- 0.44 VTD/s vs 2.74 +/- 0.46 VTD/s; peak filling rate 2.72 +/- 0.54 VTD/s vs 2.6 +/- 0.58 VTD/s) did not show significant changes after treatment. In conclusion, our results suggest that epidoxorubicin administration using the "high-dose short-term" protocol in patients with breast cancer does not induce early significant abnormalities of left ventricular systolic and diastolic function.

Antibiotics, Antineoplastic↗
PubMed1996

Molecular cloning and expression analysis of the human Rab7 GTP-ase complementary deoxyribonucleic acid.

Rab7 is a small GTP-ase localized on late endosomes, which regulates late endocytic membrane traffic in mammalian cells. Moreover it has been shown that this protein has a fundamental role in the cellular vacuolation induced by the cytotoxin VacA of Helicobacter pylori. We report here for the first time the isolation of a cDNA encoding human Rab7 from a placenta cDNA library. The open reading frame for human Rab7 encodes a protein of 207 amino acids which exhibits high homology with the mouse, rat, and dog counterparts. Northern blot analysis of total RNAs isolated from different cell lines with a cDNA probe containing the entire open reading frame revealed two mRNA transcripts of 2.5 and 1.8 kilobases. The isolation of human Rab7 cDNA will allow further characterization of its function in normal and pathological states.

Amino Acid Sequence↗
PubMed1996

Assessment of myocardial viability in patients with chronic coronary artery disease. Rest-4-hour-24-hour 201Tl tomography versus dobutamine echocardiography.

BACKGROUND: To date, late redistribution after resting 201Tl injection has not been evaluated. In addition, the concordance between resting 201Tl imaging and dobutamine echocardiography in identifying viable myocardium has not been assessed. METHODS AND RESULTS: Forty patients with coronary artery disease underwent rest-4-hour-24-hour 201Tl tomography and dobutamine echocardiography (5 to 10 micrograms.kg-1.min-1). Late redistribution occurred in 46 (21%) of 219 persistent defects at 4 hours. Systolic function and contractile reserve were similar among persistent defects at 4 hours with and without late redistribution. Contractile reserve was more frequent in segments with normal 201Tl uptake (59%), completely reversible defects (53%), or mild to moderate defects at 4 hours (56%) compared with severe defects (14%; P < .02 versus all). Of 105 hypokinetic segments, 99 (94%) were viable by 201Tl, and 88 (84%) showed contractile reserve. In contrast, of 155 akinetic segments, 119 (77%) were viable by 201Tl, but only 34 (22%) had contractile reserve. Concordance between 201Tl and dobutamine was 82% in hypokinetic segments but 43% in akinetic segments. In 109 revascularized segments, positive accuracy for functional recovery was 72% for 201Tl and 92% for dobutamine, whereas negative accuracy was 100% and 65%, respectively. Sensitivity was 100% for 201Tl and 79% for dobutamine. CONCLUSIONS: Late redistribution occurs in one fifth of persistent defects at 4 hours, and it does not correlate to systolic function or contractile reserve. Dobutamine and 201Tl yield concordant information in the majority of hypokinetic segments, whereas concordance is low in akinetic segments. Dobutamine demonstrates higher positive accuracy and sensitivity in predicting recovery of dysfunctional myocardium, whereas 201Tl shows higher negative predictive accuracy but reduced positive accuracy.

Aged↗
PubMed1996

Prolonged impairment of regional contractile function after resolution of exercise-induced angina. Evidence of myocardial stunning in patients with coronary artery disease.

BACKGROUND: Delayed recovery of contractile function in spite of normal perfusion (ie, "stunning") has been described in animal models of exercise-induced myocardial ischemia. Therefore, we investigated whether stunning may result from effort angina in patients. METHODS AND RESULTS: Patients with coronary artery disease underwent exercise testing combined with quantitative measurements of contractile function for up to 240 minutes after exercise determined by either measurement of regional ejection fraction (99mTc radionuclide angiography; n = 17, group A) or computer-assisted measurement of systolic wall thickening (n = 14, group B). In the latter group, myocardial perfusion was also evaluated by 99mTc-sestamibi tomographic imaging. Angina induced marked contractile dysfunction. Hemodynamic and ECG changes brought about by ischemia were promptly normalized. Furthermore, no perfusion defects could be detected in group B patients 30 minutes after exercise, yet contractile function remained impaired well after cessation of exercise. Thirty minutes into recovery, regional ejection fraction of previously ischemic areas was still 82.6 +/- 4.6% of baseline in group A (P < .05). Similarly, in group B patients, systolic thickening of previously ischemic segments was still significantly impaired 60 minutes after exercise, averaging 33.8 +/- 2.8% versus 40.5 +/- 2.7% at baseline (P < .05). Contractile impairment was fully reversible, as the functioning of previously ischemic segments normalized between 60 and 120 minutes of recovery. CONCLUSIONS: Prolonged yet ultimately reversible impairment of regional myocardial function may occur in patients after exercise-induced angina in the absence of perfusion abnormalities. These findings indicate that myocardial stunning may ensue after effort angina in patients with severe coronary artery disease.

Adult↗