[Efficacy of rotational atherectomy].
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Biomedical subjects
Publications and source records attributed to R Moreno.
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Alpha-fetoprotein and fetal serum albumin have been simultaneously purified from fetal bovine serum by mild procedures utilizing ammonium sulfate, hydrophobic interaction, immobilized metal (nickel) affinity chromatography, and isoelectric focusing. The lipidic extract from each protein was analyzed by gas chromatography and the peak appearing just after the arachidonic acid was identified as squalene by gas chromatography-mass spectrometry. This isoprenoid was not detected formerly in these proteins from human, rat, bovine, and pig. Until recently, in the analysis of the fatty acid composition of the alpha-fetoprotein and serum albumin from mammals, a peak has been assigned in the last part of the chromatographic profile, after arachidonic acid, to docosahexaenoic acid. In the present work, it was found that the peak corresponds to squalene instead of docosahexaenoic acid. Furthermore, we conclude that bovine alpha-fetoprotein and fetal serum albumin carry squalene, but not docosahexaenoic acid. These results agree with others obtained analyzing the same proteins from chick embryo.
AIM: To establish the value of alanine aminotransferase normalization and hepatitis C virus-RNA clearance as predictors of sustained virological response in naïve and relapser chronic hepatitis C patients on mono or combination therapy. METHODS: A total of 282 hepatitis C patients were studied: 98 naïves on interferon, and 64 naïves and 75 relapsers on interferon plus oral ribavirin; 45 patients were excluded. Drugs were administered at standard doses for 12 months. Alanine aminotransferase and hepatitis C virus-RNA were determined at baseline and at weeks 4, 12, 24, 48, and at 72 and 96 weeks after completion of therapy. RESULTS: The rate of sustained response was greater (P < 0.05) in naïves and relapsers on combination therapy (33% and 48%, respectively) than in naïves on interferon alone (16%). Hepatitis C virus-RNA significantly decreased from baseline by week 4 in naïves on interferon and relapsers on combination therapy and by week 12 in naïves on combination therapy. Alanine aminotransferase levels paralleled viremic load in naïves on interferon, yet in patients on combination therapy, alanine aminotransferase normalized independently of the virological response. During treatment, the main factor associated with sustained response was hepatitis C virus-RNA clearance by week 4 in naïves on interferon and relapsers on combination therapy, and by week 24 in naïves on combination therapy. CONCLUSION: Clearance of viraemia constitutes the best predictor of a sustained response to therapy, but needs to be measured at patient-specific times.
The interaction between zona pellucida polysulphates and sperm receptors appears to be a widespread mechanism used by mammals during gamete interaction. In this work, the effect of heparin on binding, penetration and fertilization of mouse and hamster oocytes was assessed. We found that heparin inhibited oocyte penetration and fertilization in both species. Heparin as well as fucoidan (a fucose-sulphate polymer) inhibited the proteolytic activity of acrosomal enzymes in both species. Our results suggest that zona pellucida penetration in both species may be modulated by polysulphates acting on either the proteolytic rate of degradation of the zona and/or its interaction with acrosome-reacted sperm (secondary binding).
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Since the development of the first general outcome prediction models, these instruments have been widely used in the intensive care unit (ICU), both for patient evaluation and for ICU evaluation. Since some of these uses have been serious questioned, we assisted in the last years to the exploration of alternative paths for increasing the predictive power of the models and to enhance their applicability and utility in the real world. Part of these efforts focused on the exploration of more meaningful outcomes (clinical and non-clinical) with a strong tonic into the relation between outcomes and resources use. Also, since it is now widely recognized that the ICU is not an island, but it is integrated in a continuum of care, more and more efforts are being made to optimize and evaluate the interface between the ICU and the hospital, both at ICU admission and at ICU discharge. The objective of this review is to present and discuss, to the clinician working in the ICU, these emerging issues.
Monoclonal antibodies (MAbs) specific for Plasmodium falciparum rhoptry-associated protein 1 (RAP-1) were generated and tested for inhibition of parasite growth in vitro. The majority of indirect immunofluorescence assay (IFA)-positive MAbs raised against recombinant RAP-1 positions 23 to 711 (rRAP-1(23-711)) recognized epitopes located in the immunodominant N-terminal third of RAP-1. MAbs specific for the building block 35.1 of the synthetic peptide malaria vaccine SPf66 also yielded an IFA staining pattern characteristic for rhoptry-associated proteins and reacted specifically with rRAP-1 and parasite-derived RAP-1 molecules p67 and p82. Cross-reactivity with RAP-1 was blocked by the 35.1 peptide. Epitope mapping with truncated rRAP-1 molecules and overlapping peptides identified the linear RAP-1 sequence Y218KYSL222 as a target of the anti-35.1 MAbs. This sequence lacks primary sequence similarity with the 35.1 peptide (YGGPANKKNAG). Cross-reactivity of the anti-35.1 MAbs thus appears to be associated with conformational rather than sequence homology. While the anti-35.1 MAb SP8.18 exhibited parasite growth-inhibitory activity, none of the tested anti-rRAP-1(23-711) MAbs inhibited parasite growth, independently of their fine specificity for the RAP-1 sequences at positions 33 to 42, 213 to 222, 243 to 247, 280 to 287, or 405 to 446. The growth-inhibitory activity of MAb SP8.18 was, however, accelerated by noninhibitory anti-RAP-1 MAbs. Results demonstrate that in addition to fine specificity, other binding parameters are also crucial for the inhibitory potential of an antibody.
Administration of bleomycin into the lungs of experimental animals has been utilized as a model to understand human pulmonary fibrosis. Most of the studies, however, have focused on early stages of the lung reaction. We hypothesized that chronic stages of the model may not mimic idiopathic pulmonary fibrosis, since in preliminary studies, lung volume and compliance were not decreased. Eight male Sprague-Dawley rats receiving intratracheal bleomycin (0.5 U/100 g body weight) underwent measurement of FRC, inspiratory capacity, and lung compliance 120 d later. Lung histologic changes were evaluated using light microscopy. Eight rats without intervention served as controls. Results show that our model, in early stages, has histologic changes no different from those previously described elsewhere. In chronic stages, however, the model does not behave as a restrictive syndrome: FRC is normal or increased, whereas lung compliance is normal. Focal peribronchiolar inflammation and fibrosis associated with paracicatricial emphysematous changes are the main histologic features of long-term lung remodeling after bleomycin. We conclude that while the chronic stages of the model may be informative in understanding mechanisms of fibrosis, care should be taken not to extrapolate to human idiopathic pulmonary fibrosis. We speculate that the model might resemble a particular subgroup of human interstitial lung disease, namely, those involving peribronchiolar structures.
The normal structure and function of sperm are prerequisites for successful fertilization and embryonic development, but little is known about how defective sperm are eliminated during mammalian spermatogenesis. Here, we describe a ubiquitin-dependent, sperm quality control mechanism that resides in the mammalian epididymis, the site of sperm maturation and storage. We used immunofluorescence, electron microscopy, western blotting and pulse-chase experiments to show that ubiquitin is secreted by the epididymal epithelium and binds to the surface of defective sperm. Most of the ubiquitinated sperm are subsequently phagocytosed by the epididymal epithelial cells. A portion of defective sperm escapes phagocytosis and can be found in the ejaculate. Cultured epididymal cells maintain their ability to produce ubiquitin and phagocytose the defective sperm, as well as the ubiquitin-coated microspheres, in vitro. The surprising phenomenon of cell-surface ubiquitination in defective sperm provides a possible mechanism for sperm quality control in mammals and a new marker of semen abnormalities in men and animals.
BACKGROUND AND OBJECTIVE: In vessels with moderate-severe tortuosity, rigidity or calcium, 6 French guiding catheters may be of help in stent delivering, allowing a deep coronary intubation and, hence, an easier coronary stent advancement. In this study, we describe our experience in coronary stenting using 5 French guiding catheters. METHODS AND RESULTS: The study population is constituted by 46 patients in whom coronary stenting was attempted through a 5 French guiding catheter. Sixty-six stents were delivered in 56 vessels; the 5 French Zuma guiding catheter (MedtronicAVE, Minneapolis, Minnesota) was used. In 74% of cases, a moderate-severe tortuosity was present, and calcium was visible by fluoroscopy in 27%. The stented lesions were de novo in 95%, and 42% of stents were placed in the right coronary artery. The stent was successfully delivered and implanted in all but one case (98.5%). In one patient with severe vessel tortuosity, a successful balloon dilation was performed, but the stent could not be successfully advanced through the coronary artery to the left anterior descending, and could be retrieved without any complication. Changing to a larger size guiding catheter was not required in any patient. Balloon predilation was performed before coronary placement in 41 of the 66 stents (62.1%), whereas stents were directly implanted without balloon predilation in the remaining 25 cases (37.9%). CONCLUSION: Coronary stenting through 5 French guiding catheters is feasible. This strategy may be especially indicated in patients with moderate-severe vessel tortuosity.
BACKGROUND AND OBJECTIVES: Administration of dipyridamole produces angina and ST depression in 20%-30% and 6%-34% of patients, respectively. This study aimed to evaluate the clinical implications of the presentation of angina and/or ST depression during the administration of dipyridamole in the study of coronary heart disease by myocardial perfusion SPECT (MPS). METHODS: The study population is constituted by 593 consecutive patients without left branch block or ventricular pacemaker rhythm who were referred to our service to undergo MPS with dipyridamole. A SPECT was performed after the administration of 99mTc-tetrosfosmine and drug stimulation with dipyridamole (0.142 mg/kg/min for 4 minutes). A coronariography was performed in 338 patients (57%). The frequency of clinical and electrical positivity and their relationship with the MPS and the coronariography were studied. RESULTS: The rate of angina and ST depression was 32% (n = 190) and 10% (n = 58), respectively. Myocardial perfusion defects were observed in 465 patients (78%), and signs of scintigraphic ischemia in 311 (52%). The patients with ST depression presented a higher frequency of perfusion defects (93% vs 76%, p = 0.0012) and scintigraphic ischemia (89% vs 49%, p < 0.0001). In addition, perfusion defects in more than one territory were observed in these patients in a higher percentage (53% vs 34%, p = 0.0036). Among the patients who underwent cardiac catheterization, those who had a ST depression had a greater extension of coronary heart disease (1.8 +/- 1.2 vs 1.3 +/- 1.0 diseased vessels, respectively. p = 0.0100) and a higher frequency of multivessel disease (61% vs 43%, p = 0.0380). Those patients who had clinical positivity showed a scintigraphic ischemia more frequently (66% vs 47%, p < 0.0001), however no statistically significant differences were observed between the presence of patients with perfusion defects or in the extension of these defects as well as in the number of diseased vessels in the coronariographic study. CONCLUSIONS: During the administration of dipyridamole, the ST depression is associated with more frequent scintigraphic ischemia, larger extension of perfusion defects and more diseased vessels. The appearance of angina is associated with scintigraphic ischemia, but it is not necessarily associated with the extension of perfusion defects or greater number of diseased vessels.
AIMS: The objective of this study was to report the experience in the treatment of acute myocardial infarction (AMI) with early coronary angioplasty (PTCA) in a single European center during one decade, attempting to identify the characteristics associated with a poor prognosis in these patients. METHODS AND RESULTS: Eight hundred patients with AMI were treated with PTCA < 12 hours after symptom onset. Mean age was 64 +/- 13 years, 12% were in cardiogenic shock, AMI location was anterior in 61% and PTCA was performed after failed thrombolysis in 5%. Coronary stents and abciximab were used in 51% and 10%, respectively. An angiographic successful result was obtained in 93%, and final TIMI flow grade 3 was achieved in 83%. The overall in-hospital mortality rate was 12.5% (2.7%, 16.1%, 25.7% and 63.8% in patients in Killip class I, II, III and IV, respectively). Over the years, an improvement in the angiographic results and a reduction in the rates of reinfarction and target vessel revascularization were observed. The independent predictors of death were age > 70 years, absence of hyper-cholesterolemia, anterior location, cardiogenic shock, multi-vessel disease and unsuccessful PTCA. The leading causes of mortality were cardiogenic shock (63%) and ventricular free wall rupture (14%). The rates of non-fatal reinfarction, documented reocclusion and in-hospital repeated revascularization were 2%, 3% and 4%, respectively. CONCLUSION: In most cases, PTCA performed in a non-selected patient population with AMI results in angiographic success. Mortality especially occurs in patients who are in cardiogenic shock at the beginning of the procedure. We have observed an improvement in the results throughout the course of the decade.
A total of 590 patients with myocardial infarction treated with primary angioplasty were studied, to assess the incidence and related factors of free-wall rupture in patients with acute myocardial infarction when treated with primary angioplasty. The incidence of free-wall rupture was 2.2% (13 patients); this incidence was higher in patients >65 years old, women, nonsmokers, as well as in those with anterior location and an initial TIMI grade 0 flow, but it was similar in patients with a successful or unsuccessful angiographic result.
OBJECTIVES: To describe risk factors for the development of acute renal failure (ARF) in a population of intensive care unit (ICU) patients, and the association of ARF with multiple organ failure (MOF) and outcome using the sequential organ failure assessment (SOFA) score. DESIGN: Prospective, multicenter, observational cohort analysis. SETTING: Forty ICUs in 16 countries. PATIENTS: All patients admitted to one of the participating ICUs in May 1995, except those who stayed in the ICU for less than 48 h after uncomplicated surgery, were included. After the exclusion of 38 patients with a history of chronic renal failure requiring renal replacement therapy, a total of 1411 patients were studied. MEASUREMENTS AND RESULTS: Of the patients, 348 (24.7%) developed ARF, as diagnosed by a serum creatinine of 300 micromol/l (3.5 mg/dl) or more and/or a urine output of less than 500 ml/day. The most important risk factors for the development of ARF present on admission were acute circulatory or respiratory failure; age more than 65 years, presence of infection, past history of chronic heart failure (CHF), lymphoma or leukemia, or cirrhosis. ARF patients developed MOF earlier than non-ARF patients (median 24 vs 48 h after ICU admission, p < 0.05). ARF patients older than 65 years with a past history of CHF or with any organ failure on admission were most likely to develop MOF. ICU mortality was 3 times higher in ARF than in other patients (42.8% vs 14.0%, p < 0.01). Oliguric ARF was an independent risk factor for overall mortality as determined by a multivariate regression analysis (OR = 1.59 [CI 95%: 1.23-2.06], p < 0.01). Infection increased the risk of death associated with all factors. Factors that increased the ICU mortality of ARF patients were a past history of hematologic malignancy, age more than 65 years, the number of failing organs on admission and the presence of acute cardiovascular failure. CONCLUSION: In ICU patients, the most important risk factors for ARF or mortality from ARF are often present on admission. During the ICU stay, other organ failures (especially cardiovascular) are important risk factors. Oliguric ARF was an independent risk factor for ICU mortality, and infection increased the contribution to mortality by other factors. The severity of circulatory shock was the most important factor influencing outcome in ARF patients.
The objective of the study was to evaluate the results of the myocardial scintigraphy with 99mTc-tetrofosmin (Tc-Tf) and pharmacological stimulation with dipyridamole in patients diagnosed of microvascular angina. The study population is made up of 50 patients discharged with the diagnosis of microvascular angina who had undergone Tc-Tf-dipyridamole. Clinical and electrical positivity appeared in 40% and 12% of the patients, respectively. Myocardial perfusion defects were found in 35 patients (70%), and were reversible in 21 (60%), fixed in 11 (21%), and combined in 3 (9%). Abnormalities were inferior, anteroseptal and lateral in 21, 18, and 2 patients, respectively. Patients with a positive exercise treadmill test, compared with those with a negative one, had more frequent perfusion abnormalities (91% vs 50%, p = 0.0327) and myocardial ischemia (64% vs 20%, p = 0.392). Women, in comparison with men, had angina (56% vs 22%, p = 0.013), and anteroseptal perfusion abnormalities (26% vs 4%, p = 0.028) more frequently. On the contrary, men had inferior perfusion abnormalities more frequently (57% vs 30%, p = 0.057). Thus, Tc-Tf-dipyridamole shows perfusion abnormalities in 70% of patients with microvascular angina (91% in patients with a positive exercise treadmill test). Scintigraphic pattern may be partially conditioned by gender in these patients.
OBJECTIVE: To describe the angiographic results and the in-hospital clinical outcome of patients with an acute phase of myocardial infarction treated with coronary angioplasty and stent placement. METHODS: 268 patients with myocardial infarction were treated with angioplasty and coronary stenting within in our center 12 hours after the onset of symptoms from January in 1992 to March 1998. 366 stents were placed (1.4 +/- 0.7 per patient), 35% being Palmaz-Schatz, 26% Wiktor, 21% Multi-Link and 18% others. Stenting was elective in 171 patients (64%), and the majority of patients (91%) were treated with aspirin plus ticlopidine. RESULTS: A successful angiographic result was achieved in 258 patients (96%). Minimum lumen diameter was increased from 0.2 +/- 0.3 to 2.7 +/- 0.7 mm (p < 0.001), and stenosis decreased from 94 +/- 8% to 13 +/- 11% (p < 0.001). Mortality was 15.3% (3.2%, 24.4% and 67.7% in patients in Killip class I, II-III and IV, respectively). Nonfatal reinfarction and recurrent ischemia rates were 2.6% and 9%, respectively. Stent thrombosis occurred in 8 patients (3.0%), and new target vessel revascularization was needed in 12 (4.5%). CONCLUSIONS: Stent placement in acute myocardial infarction is associated with high angiographic success rate, as well as a good in-hospital outcome. Mortality is localized, especially in patients with cardiac failure at the beginning of the procedure.
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INTRODUCTION: In patients with acute myocardial infarction treated with primary angioplasty, the inability to achieve successful coronary reperfusion is associated with higher mortality. The objective of the study was to identify which characteristics may predict a lower angiographic success rate in patients with acute myocardial infarction treated with coronary angioplasty. PATIENTS AND METHODS: The study population is constituted by the 790 patients with acute myocardial infarction that were treated with angioplasty within the 12 hours after the onset of symptoms from 1991 to 1999 at our institution. A successful angiographic result was considered in presence of a residual stenosis < 50% and a TIMI flow 2 or 3 after the procedure. RESULTS: A successful angiographic result and a final TIMI 3 flow were achieved in 736 (93.2%) and 652 (82.5%) patients, respectively. In-hospital mortality was higher in patients with angiographic failure than in those with angiographic successful result (48 vs. 10%; p < 0.01). Age under 65 (91 vs. 95%; p = 0.02), non smoking (90 vs. 96%; p < 0,01), previous infarction (87 vs. 94%; p < 0.01), angioplasty after failed thrombolysis (83 vs. 94%; p = 0. 02), cardiogenic shock (80 vs. 95%; p < 0.01), undetermined location (67 vs. 93%; p < 0.01), non-inferior location (92 vs. 96%; p = 0.04), left bundle branch block (64 vs. 94%; p < 0.01), multivessel disease (91 vs. 95%; p = 0.02), left ventricular ejection fraction < 0.40 (89 vs. 97%; p < 0.01), no utilization of coronary stenting (90 vs. 96%; p < 0.01), and use of intraaortic balloon counterpulsation pump (82 vs. 95%; p < 0.01) were associated with a lower angiographic success rate. In the multivariable analysis, the following were independent predictors for angiographic failure: left bundle branch block (odds ratio [OR], 12.95; CI 95%, 3.00-53.90), cardiogenic shock (OR, 4.20; CI 95%, 1.95-8.75), no utilization of coronary stent (OR, 3.44; CI 95%, 1.71-7.37), and previous infarction (OR, 2.82; CI 95%, 1.29-5.90). CONCLUSIONS: Coronary angioplasty allows a successful coronary recanalization in most patients with acute myocardial infarction. Some basic characteristics, however, may identify some subsets in which a successful angiographic result may be more difficult to obtain.